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Genetic Manipulation of Streptococcus pyogenes (The Group A Streptococcus, GAS)
Le Breton, Yoann; McIver, Kevin S.
Streptococcus pyogenes (the group A streptococcus, GAS) is a Gram-positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe often life-threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutagenesis, and genetic complementation. PMID:24510894
Complete Genome of Acute Rheumatic Fever-Associated Serotype M5 Streptococcus pyogenes Strain Manfredo
Matthew T. G. Holden; Annabel Scott; Inna Cherevach; Tracey Chillingworth; Carol Churcher; Ann Cronin; Linda Dowd; Theresa Feltwell; Nancy Hamlin; Simon Holroyd; Kay Jagels; Sharon Moule; Karen Mungall; Michael A. Quail; Claire Price; Ester Rabbinowitsch; Sarah Sharp; Jason Skelton; Sally Whitehead; Bart G. Barrell; Michael Kehoe; Julian Parkhill
Comparisons of the 1.84-Mb genome of serotype M5 Streptococcus pyogenes strain Manfredo with previously sequenced genomes emphasized the role of prophages in diversification of S. pyogenes and the close relationship between strain Manfredo and MGAS8232, another acute rheumatic fever-associated strain. Streptococcus pyogenes (alternatively referred to as group A Streptococcus) is responsible for diverse diseases in humans, including pharyngitis, toxic shock
A Rare Cause of Endocarditis: Streptococcus pyogenes.
Ye?ilkaya, Ay?egül; Azap, Ozlem Kurt; Pirat, Bahar; Gültekin, Bahad?r; Arslan, Hande
Although group A ?-hemolytic streptococcus is an uncommon cause of infective endocarditis, an increase in the incidence of invasive group A streptococcus infections including bacteremia has been reported in the last two decades. Herein we report Streptococcus pyogenes endocarditis in a previously healthy adult patient who was hospitalized to investigate the etiology of fever. Because of a suspicion of a new vegetation appeared in the second (aortic) valve in the 14(th) day of high dose penicillin G treatment, the mitral and aortic valves were replaced by mechanical prosthesis on the 22(nd) day of treatment. He was discharged from hospital after the 6 week course of antibiotic treatment. PMID:25207027
A Rare Cause of Endocarditis: Streptococcus pyogenes
Ye?ilkaya, Ay?egül; Azap, Özlem Kurt; Pirat, Bahar; Gültekin, Bahad?r; Arslan, Hande
Although group A ?-hemolytic streptococcus is an uncommon cause of infective endocarditis, an increase in the incidence of invasive group A streptococcus infections including bacteremia has been reported in the last two decades. Herein we report Streptococcus pyogenes endocarditis in a previously healthy adult patient who was hospitalized to investigate the etiology of fever. Because of a suspicion of a new vegetation appeared in the second (aortic) valve in the 14th day of high dose penicillin G treatment, the mitral and aortic valves were replaced by mechanical prosthesis on the 22nd day of treatment. He was discharged from hospital after the 6 week course of antibiotic treatment. PMID:25207027
Laboratory Growth and Maintenance of Streptococcus pyogenes (The Group A Streptococcus, GAS)
Gera, Kanika; McIver, Kevin S.
Streptococcus pyogenes is a Gram-positive bacterium that strictly infects humans. It is the causative agent of a broad spectrum of diseases accounting for millions of infections and at least 517, 000 deaths each year worldwide (Carapetis et al., 2005). It is a nutritionally fastidious organism that ferments sugars to produce lactic acid and has strict requirements for growth. To aid in the study of this organism, this unit describes the growth and maintenance of S. pyogenes. PMID:24510893
Complete Genome Sequence of emm Type 14 Streptococcus pyogenes Strain HSC5
Port, Gary C.; Paluscio, Elyse
Streptococcus pyogenes causes a greater diversity of human disease than any other bacterial pathogen. Here, we present the complete genome sequence of the emm type 14 S. pyogenes strain HSC5. This strain is a robust producer of the cysteine protease SpeB and is capable of producing infection in several different animal models. PMID:23950122
CRISPR Inhibition of Prophage Acquisition in Streptococcus pyogenes
Takashi Nozawa; Nayuta Furukawa; Chihiro Aikawa; Takayasu Watanabe; Bijaya Haobam; Ken Kurokawa; Fumito Maruyama; Ichiro Nakagawa
Streptococcus pyogenes, one of the major human pathogens, is a unique species since it has acquired diverse strain-specific virulence properties mainly through the acquisition of streptococcal prophages. In addition, S. pyogenes possesses clustered regularly interspaced short palindromic repeats (CRISPR)\\/Cas systems that can restrict horizontal gene transfer (HGT) including phage insertion. Therefore, it was of interest to examine the relationship between
The Streptococcus pyogenes proteome: maps, virulence factors and vaccine candidates
Dmitriev, Alexander V; Chaussee, Michael S
Streptococcus pyogenes is an important cause of human morbidity and mortality worldwide. A wealth of genomic information related to this pathogen has facilitated exploration of the proteome, particularly in response to environmental conditions thought to mimic various aspects of pathogenesis. Proteomic approaches are also used to identify immunoreactive proteins for vaccine development and to identify proteins that may induce autoimmunity. These studies have revealed new mechanisms involved in regulating the S. pyogenes proteome, which has opened up new avenues in the study of S. pyogenes pathogenesis. This article describes the methods used, and progress being made towards characterizing the S. pyogenes proteome, including studies seeking to identify potential vaccine candidates. PMID:21073313
Molecular Epidemiology of sil Locus in Clinical Streptococcus pyogenes Strains
Plainvert, Céline; Dinis, Márcia; Ravins, Miriam; Hanski, Emanuel; Touak, Gérald; Dmytruk, Nicolas; Fouet, Agnčs
Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the sil locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that sil prevalence is around 15%; furthermore, whereas a correlation between the presence of sil and the genetic background was suggested, no link between the presence of a functional sil locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all emm genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were sil positive. The prevalence of the sil locus varied according to the emm genotype, being present in >85% of the emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1, emm28, and emm89 strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are sil positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional sil system. No correlation was observed between the presence or absence of a functional sil locus and the strain invasiveness status. PMID:24671796
CRISPR inhibition of prophage acquisition in Streptococcus pyogenes.
Nozawa, Takashi; Furukawa, Nayuta; Aikawa, Chihiro; Watanabe, Takayasu; Haobam, Bijaya; Kurokawa, Ken; Maruyama, Fumito; Nakagawa, Ichiro
Streptococcus pyogenes, one of the major human pathogens, is a unique species since it has acquired diverse strain-specific virulence properties mainly through the acquisition of streptococcal prophages. In addition, S. pyogenes possesses clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems that can restrict horizontal gene transfer (HGT) including phage insertion. Therefore, it was of interest to examine the relationship between CRISPR and acquisition of prophages in S. pyogenes. Although two distinct CRISPR loci were found in S. pyogenes, some strains lacked CRISPR and these strains possess significantly more prophages than CRISPR harboring strains. We also found that the number of spacers of S. pyogenes CRISPR was less than for other streptococci. The demonstrated spacer contents, however, suggested that the CRISPR appear to limit phage insertions. In addition, we found a significant inverse correlation between the number of spacers and prophages in S. pyogenes. It was therefore suggested that S. pyogenes CRISPR have permitted phage insertion by lacking its own spacers. Interestingly, in two closely related S. pyogenes strains (SSI-1 and MGAS315), CRISPR activity appeared to be impaired following the insertion of phage genomes into the repeat sequences. Detailed analysis of this prophage insertion site suggested that MGAS315 is the ancestral strain of SSI-1. As a result of analysis of 35 additional streptococcal genomes, it was suggested that the influences of the CRISPR on the phage insertion vary among species even within the same genus. Our results suggested that limitations in CRISPR content could explain the characteristic acquisition of prophages and might contribute to strain-specific pathogenesis in S. pyogenes. PMID:21573110
Streptococcus pyogenes biofilms—formation, biology, and clinical relevance
Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd
Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options. PMID:25717441
Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification
Towers, Rebecca J.; Carapetis, Jonathan R.; Currie, Bart J.; Davies, Mark R.; Walker, Mark J.; Dougan, Gordon; Giffard, Philip M.
The Indigenous population of the Northern Territory of Australia (NT) suffers from a very high burden of Streptococcus pyogenes disease, including cardiac and renal sequelae. The aim of this study was to determine if S. pyogenes isolated from this population represent NT endemic strains, or conversely reflect strains with global distribution. emm sequence typing data were used to select 460 S. pyogenes isolates representing NT S. pyogenes diversity from 1987–2008. These isolates were genotyped using either multilocus sequence typing (MLST) or a high resolution melting-based MLST surrogate (Minim typing). These data were combined with MLST data from other studies on NT S. pyogenes to yield a set of 731 MLST or Minim typed isolates for analysis. goeBURST analysis of MLST allelic profiles and neighbour-joining trees of the MLST allele sequences revealed that a large proportion of the known global S. pyogenes MLST-defined diversity has now been found in the NT. Specifically, fully sequence typed NT isolates encompass 19% of known S. pyogenes STs and 43% of known S. pyogenes MLST alleles. These analyses provided no evidence for major NT-endemic strains, with many STs and MLST alleles shared between the NT and the rest of the world. The relationship between the number of known Minim types, and the probability that a Minim type identified in a calendar year would be novel was determined. This revealed that Minim types typically persist in the NT for >1 year, and indicate that the majority of NT Minim types have been identified. This study revealed that many diverse S. pyogenes strains exhibit global scale mobility that extends to isolated populations. The burden of S. pyogenes disease in the NT is unlikely to be due to the nature of NT S. pyogenes strains, but is rather a function of social and living conditions. PMID:24066079
Proteomic Analysis and Identification of Streptococcus pyogenes Surface-Associated Proteins?
Severin, Anatoly; Nickbarg, Elliott; Wooters, Joseph; Quazi, Shakey A.; Matsuka, Yury V.; Murphy, Ellen; Moutsatsos, Ioannis K.; Zagursky, Robert J.; Olmsted, Stephen B.
Streptococcus pyogenes is a gram-positive human pathogen that causes a wide spectrum of disease, placing a significant burden on public health. Bacterial surface-associated proteins play crucial roles in host-pathogen interactions and pathogenesis and are important targets for the immune system. The identification of these proteins for vaccine development is an important goal of bacterial proteomics. Here we describe a method of proteolytic digestion of surface-exposed proteins to identify surface antigens of S. pyogenes. Peptides generated by trypsin digestion were analyzed by multidimensional tandem mass spectrometry. This approach allowed the identification of 79 proteins on the bacterial surface, including 14 proteins containing cell wall-anchoring motifs, 12 lipoproteins, 9 secreted proteins, 22 membrane-associated proteins, 1 bacteriophage-associated protein, and 21 proteins commonly identified as cytoplasmic. Thirty-three of these proteins have not been previously identified as cell surface associated in S. pyogenes. Several proteins were expressed in Escherichia coli, and the purified proteins were used to generate specific mouse antisera for use in a whole-cell enzyme-linked immunosorbent assay. The immunoreactivity of specific antisera to some of these antigens confirmed their surface localization. The data reported here will provide guidance in the development of a novel vaccine to prevent infections caused by S. pyogenes. PMID:17142387
Assessment of Streptococcus pyogenes microcolony formation in infected skin by confocal laser scanning microscopy
Hisanori Akiyama; Shin Morizane; Osamu Yamasaki; Takashi Oono; Keiji Iwatsuki
Background:Streptococcus pyogenes and Staphylococcus aureus are often simultaneously detected from many cases of non-bullous impetigo with atopic dermatitis. Objectives: Using confocal laser scanning microscopy (CLSM), to investigate formation of S. pyogenes microcolonies in skin lesions. Methods: The S. pyogenes cells in the stationary growth phase alone were strongly stained with fluorescein isothiocyanate-concanavalin A (FITC-ConA), and this staining was reduced by
Intracellular Streptococcus pyogenes in Human Macrophages Display an Altered Gene Expression Profile
Erika Hertzén; Linda Johansson; Rita Kansal; Alexander Hecht; Samira Dahesh; Marton Janos; Victor Nizet; Malak Kotb; Anna Norrby-Teglund
Streptococcus pyogenes is an important human pathogen, which has recently gained recognition as an intracellular microorganism during the course of severe invasive infections such as necrotizing fasciitis. Although the surface anchored M protein has been identified as a pivotal factor affecting phagosomal maturation and S. pyogenes survival within macrophages, the overall transcriptional profile required for the pathogen to adapt and
Murine Vaginal Colonization Model for Investigating Asymptomatic Mucosal Carriage of Streptococcus pyogenes
Watson, Michael E.; Nielsen, Hailyn V.; Hultgren, Scott J.
While many virulence factors promoting Streptococcus pyogenes invasive disease have been described, specific streptococcal factors and host properties influencing asymptomatic mucosal carriage remain uncertain. To address the need for a refined model of prolonged S. pyogenes asymptomatic mucosal colonization, we have adapted a preestrogenized murine vaginal colonization model for S. pyogenes. In this model, derivatives of strains HSC5, SF370, JRS4, NZ131, and MEW123 established a reproducible, asymptomatic colonization of the vaginal mucosa over a period of typically 3 to 4 weeks' duration at a relatively high colonization efficiency. Prior treatment with estradiol prolonged streptococcal colonization and was associated with reduced inflammation in the colonized vaginal epithelium as well as a decreased leukocyte presence in vaginal fluid compared to the levels of inflammation and leukocyte presence in non-estradiol-treated control mice. The utility of our model for investigating S. pyogenes factors contributing to mucosal carriage was verified, as a mutant with a mutation in the transcriptional regulator catabolite control protein A (CcpA) demonstrated significant impairment in vaginal colonization. An assessment of in vivo transcriptional activity in the CcpA? strain for several known CcpA-regulated genes identified significantly elevated transcription of lactate oxidase (lctO) correlating with excessive generation of hydrogen peroxide to self-lethal levels. Deletion of lctO did not impair colonization, but deletion of lctO in a CcpA? strain prolonged carriage, exceeding even that of the wild-type strain. Thus, while LctO is not essential for vaginal colonization, its dysregulation is deleterious, highlighting the critical role of CcpA in promoting mucosal colonization. The vaginal colonization model should prove effective for future analyses of S. pyogenes mucosal colonization. PMID:23460515
Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.
Ong, Cheryl-Lynn Y; Walker, Mark J; McEwan, Alastair G
Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways. PMID:26028191
Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes
Ong, Cheryl-lynn Y.; Walker, Mark J.; McEwan, Alastair G.
Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways. PMID:26028191
Expression of the Secondary Sigma Factor X in Streptococcus pyogenes Is Restricted at Two Levels
Jason A. Opdyke; June R. Scott; Charles P. Moran
Secondary RNA polymerase sigma factors in many bacteria are responsible for regulating a vast range of processes including virulence. A protein (X) in the gram-positive human pathogen Streptococcus pyogenes (the group A Streptococcus or GAS) was recently shown to function in vitro as a secondary sigma factor. We report here the isolation of a mutant in which both sigX genes
Closed Genome Sequence of Noninvasive Streptococcus pyogenes M/emm3 Strain STAB902
Paris-Sud XI, Université de
Closed Genome Sequence of Noninvasive Streptococcus pyogenes M/emm3 Strain STAB902 Nicolas Soriano Rennes 1, Rennes, Franced We report a closed genome sequence of group A Streptococcus genotype emm3 (GAS M/emm3) strain STAB902, isolated from a superficial pyodermatitis. The genome is composed of 1
Differential Recognition of Surface Proteins in Streptococcus pyogenes by Two Sortase Gene Homologs
Timothy C. Barnett; June R. Scott
The interaction of Streptococcus pyogenes (group A streptococcus (GAS)) with its human host requires several surface proteins. In this study, we isolated mutations in a gene required for the surface localization of protein F by transposon mutagenesis of the M6 strain JRS4. This gene (srtA) encodes a protein homologous to Staphylococcus aureus sortase, which covalently links proteins containing an LPXTG
Identification and Characterization of Novel Superantigens from Streptococcus pyogenes
Proft, Thomas; Louise Moffatt, S.; Berkahn, Celia J.; Fraser, John D.
Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma. A fourth novel gene (smez-2) was isolated from the S. pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene. SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin. Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively). SMEZ-2 is the most potent superantigen (SAg) discovered thus far. All toxins, except rSPE-G, were active on murine T cells, but with reduced potency. Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15–65 nM. Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II ? chain. Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G. The most common targets for the novel SAgs were human V?2.1- and V?4-expressing T cells. This might reflect a specific role for this subset of V?s in the immune defense of gram-positive bacteria. PMID:9874566
Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem
Wong, Samson SY; Yuen, Kwok-Yung
Explosive outbreaks of infectious diseases occasionally occur without immediately obvious epidemiological or microbiological explanations. Plague, cholera and Streptococcus pyogenes infection are some of the epidemic-prone bacterial infections. Besides epidemiological and conventional microbiological methods, the next-generation gene sequencing technology permits prompt detection of genomic and transcriptomic profiles associated with invasive phenotypes. Horizontal gene transfer due to mobile genetic elements carrying virulence factors and antimicrobial resistance, or mutations associated with the two component CovRS operon are important bacterial factors conferring survival advantage or invasiveness. The high incidence of scarlet fever in children less than 10 years old suggests that the lack of protective immunity is an important host factor. A high population density, overcrowded living environment and a low yearly rainfall are environmental factors contributing to outbreak development. Inappropriate antibiotic use is not only ineffective for treatment, but may actually drive an epidemic caused by drug-resistant strains and worsen patient outcomes by increasing the bacterial density at the site of infection and inducing toxin production. Surveillance of severe S. pyogenes infection is important because it can complicate concurrent chickenpox and influenza. Concomitant outbreaks of these two latter infections with a highly virulent and drug-resistant S. pyogenes strain can be disastrous. PMID:26038416
Identification and Characterization of a Streptococcus pyogenes Operon Involved in Binding of Hemoproteins and Acquisition of Iron
Christopher S. Bates; Griselle E. Montanez; Charles R. Woods; Rebecca M. Vincent; Zehava Eichenbaum
The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source. In this study, we investigate hemoprotein utilization by S. pyogenes. We demonstrate that surface proteins contribute to the binding of hemoproteins to S. pyogenes. We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein
Biofilm Formation Enhances Fomite Survival of Streptococcus pneumoniae and Streptococcus pyogenes
Marks, Laura R.; Reddinger, Ryan M.
Both Streptococcus pyogenes and Streptococcus pneumoniae are widely thought to rapidly die outside the human host, losing infectivity following desiccation in the environment. However, to date, all literature investigating the infectivity of desiccated streptococci has used broth-grown, planktonic populations. In this study, we examined the impact of biofilm formation on environmental survival of clinical and laboratory isolates of S. pyogenes and S. pneumoniae as both organisms are thought to colonize the human host as biofilms. Results clearly demonstrate that while planktonic cells that are desiccated rapidly lose viability both on hands and abiotic surfaces, such as plastic, biofilm bacteria remain viable over extended periods of time outside the host and remain infectious in a murine colonization model. To explore the level and extent of streptococcal fomite contamination that children might be exposed to naturally, direct bacteriologic cultures of items in a day care center were conducted, which demonstrated high levels of viable streptococci of both species. These findings raise the possibility that streptococci may survive in the environment and be transferred from person to person via fomites contaminated with oropharyngeal secretions containing biofilm streptococci. PMID:24371220
Vaccination with Streptococcus pyogenes nuclease A stimulates a high antibody response but no protective immunity in a mouse model of infection.
Radcliff, Fiona J; Fraser, John D; Proft, Thomas
Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic shock syndrome. Development of a vaccine for S. pyogenes has been confounded both by the diversity of the disease-causing serotypes and the spectre of inadvertently stimulating autoimmunity. The S. pyogenes nuclease A (SpnA) is a recently characterised virulence factor that is highly conserved across strains and expressed during human disease. Deletion of spnA from S. pyogenes results in reduced survival of bacteria in whole human blood and attenuated virulence in a mouse model of infection. Collectively these features suggest that SpnA has potential as a vaccine candidate for S. pyogenes. Mice vaccinated subcutaneously with single or multiple doses of recombinant SpnA emulsified in Incomplete Freund's Adjuvant developed a robust and durable IgG response, including neutralising activity, to this protein. However, vaccination with rSpnA conferred no advantage in terms of lesion development, disease symptoms or colonisation levels after a sub-lethal subcutaneous challenge with S. pyogenes. Anti-SpnA serum IgG responses and neutralising activity were increased in response to challenge, indicating that SpnA is expressed in vivo. SpnA is unlikely to be a suitable antigen for a vaccine against S. pyogenes. PMID:25119670
Antimicrobial susceptibility patterns, emm type distribution and genetic diversity of Streptococcus pyogenes recovered in Brazil
Aręas, Glauber P; Schuab, Rôde BB; Neves, Felipe PG; Barros, Rosana R
Streptococcus pyogenes is responsible for a variety of infectious diseases and immunological complications. In this study, 91 isolates of S. pyogenes recovered from oropharynx secretions were submitted to antimicrobial susceptibility testing, emm typing and pulsed-field gel electrophoresis (PFGE) analysis. All isolates were susceptible to ceftriaxone, levofloxacin, penicillin G and vancomycin. Resistance to erythromycin and clindamycin was 15.4%, which is higher than previous reports from this area, while 20.9% of the isolates were not susceptible to tetracycline. The macrolide resistance phenotypes were cMLSB (10) and iMLSB (4). The ermB gene was predominant, followed by the ermA gene. Thirty-two emm types and subtypes were found, but five (emm1, emm4, emm12, emm22, emm81) were detected in 48% of the isolates. Three new emm subtypes were identified (emm1.74, emm58.14, emm76.7). There was a strong association between emm type and PFGE clustering. A variety of PFGE profiles as well as emm types were found among tetracycline and erythromycin-resistant isolates, demonstrating that antimicrobial resistant strains do not result from the expansion of one or a few clones. This study provides epidemiological data that contribute to the development of suitable strategies for the prevention and treatment of such infections in a poorly studied area. PMID:25410998
Recombination between Streptococcus suis ICESsu32457 and Streptococcus agalactiae ICESa2603 yields a hybrid ICE transferable to Streptococcus pyogenes.
Marini, Emanuela; Palmieri, Claudio; Magi, Gloria; Facinelli, Bruna
Integrative conjugative elements (ICEs) are mobile genetic elements that reside in the chromosome but retain the ability to undergo excision and to transfer by conjugation. Genes involved in drug resistance, virulence, or niche adaptation are often found among backbone genes as cargo DNA. We recently characterized in Streptococcus suis an ICE (ICESsu32457) carrying resistance genes [tet(O/W/32/O), tet(40), erm(B), aphA, and aadE] in the 15K unstable genetic element, which is flanked by two ?1.3kb direct repeats. Remarkably, ?1.3-kb sequences are conserved in ICESa2603 of Streptococcus agalactiae 2603V/R, which carry heavy metal resistance genes cadC/cadA and mer. In matings between S. suis 32457 (donor) and S. agalactiae 2603V/R (recipient), transconjugants were obtained. PCR experiments, PFGE, and sequence analysis of transconjugants demonstrated a tandem array between ICESsu32457 and ICESa2603. Matings between tandem array-containing S. agalactiae 2603V/R (donor) and Streptococcus pyogenes RF12 (recipient) yielded a single transconjugant containing a hybrid ICE, here named ICESa2603/ICESsu32457. The hybrid formed by recombination of the left ?1.3-kb sequence of ICESsu32457 and the ?1.3-kb sequence of ICESa2603. Interestingly, the hybrid ICE was transferable between S. pyogenes strains, thus demonstrating that it behaves as a conventional ICE. These findings suggest that both tandem arrays and hybrid ICEs may contribute to the evolution of antibiotic resistance in streptococci, creating novel mobile elements capable of disseminating new combinations of antibiotic resistance genes. PMID:25935120
Analysis of beta-hemolysis in human blood agars by Streptococcus pyogenes
Kamiar Zomorodian; Mohammad Javad Rahimi; Akbar Safaei; Abdollah Bazargani; Marjan Motamadi; Mahboobeh Kharazi; Setareh Mostaghni; Keyvan Pakshir; Hamid Ghaedi; Mohammad Hossein Afsarian
The aim of the study was to assess the reliability of human blood agar media (HuBA) in identifying Streptococcus pyogenes by hemolysis analysis. We analyze several factors that might affect the accuracy of HuBA media for microbial analysis, including incubation time, blood group, Rh factor and presence of antistreptolysin-o.
Complete Genome Sequences of emm6 Streptococcus pyogenes JRS4 and Parental Strain D471
Port, Gary C.; Paluscio, Elyse
We report the complete genome assemblies of the group A Streptococcus pyogenes serotype emm6 strain D471 and its streptomycin-resistant derivative JRS4. Both of these well-studied laboratory strains have been extensively characterized over the past three decades and have been instrumental in the discovery of multiple aspects of streptococcal pathogenesis. PMID:26139722
Draft Genome Sequences of Streptococcus pyogenes Strains Associated with Throat and Skin Infections in Lebanon
Eisen, Jonathan A.; Jospin, Guillaume; Coil, David A.
We present the draft genome sequences of nine clinical Streptococcus pyogenes isolates recovered from patients suffering from sore throat and skin infections. An average of 2,454,334 paired-end reads per sample were generated, which assembled into 21 to 198 contigs, with a G+C content of 38.4 to 38.5%. PMID:24831139
Six-Month Multicenter Study on Invasive Infections Due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina
Lopardo, Horacio A.; Vidal, Patricia; Sparo, Monica; Jeric, Paola; Centron, Daniela; Facklam, Richard R.; Paganini, Hugo; Pagniez, N. Gaston; Lovgren, Marguerite; Beall, Bernard
During a 6-month period, 95 invasive infections due to Streptococcus pyogenes and group C or group G Streptococcus dysgalactiae subsp. equisimilis were recorded from 40 centers of 16 cities in Argentina. We describe here epidemiologic data available for 55 and 19 patients, respectively, associated with invasive infections due to S. pyogenes and S. dysgalactiae subsp. equisimilis. The associated isolates and 58 additional pharyngeal isolates were genotyped and subjected to serologic and/or antibiotic susceptibility testing. Group A streptococcal emm type distribution and strain association with toxic shock appeared to differ somewhat from results found within the United States; however, serologic characterization and sof sequence typing suggested that emm types found in both countries are reflective of shared clonal types. PMID:15695683
SalY of the Streptococcus pyogenes Lantibiotic Locus Is Required for Full Virulence and Intracellular Survival in Macrophages
Hilary A. Phelps; Melody N. Neely
Streptococcus pyogenes utilizes numerous mechanisms for evading the host immune response but has only recently been found to survive in the intracellular environment. In this study, we demonstrate the requirement of a putative ABC transporter permease for intracellular survival in macrophages. The highly attenuated S. pyogenes mutant, SalY, was identified from a transposon mutagenesis screen, with over 200-fold attenuation in
Multiple Roles of RNase Y in Streptococcus pyogenes mRNA Processing and Degradation
Itzek, Andreas; Malke, Horst; Ferretti, Joseph J.
Control over mRNA stability is an essential part of gene regulation that involves both endo- and exoribonucleases. RNase Y is a recently identified endoribonuclease in Gram-positive bacteria, and an RNase Y ortholog has been identified in Streptococcus pyogenes (group A streptococcus [GAS]). In this study, we used microarray and Northern blot analyses to determine the S. pyogenes mRNA half-life of the transcriptome and to understand the role of RNase Y in global mRNA degradation and processing. We demonstrated that S. pyogenes has an unusually high mRNA turnover rate, with median and mean half-lives of 0.88 min and 1.26 min, respectively. A mutation of the RNase Y-encoding gene (rny) led to a 2-fold increase in overall mRNA stability. RNase Y was also found to play a significant role in the mRNA processing of virulence-associated genes as well as in the rapid degradation of rnpB read-through transcripts. From these results, we conclude that RNase Y is a pleiotropic regulator required for mRNA stability, mRNA processing, and removal of read-through transcripts in S. pyogenes. PMID:23543715
NrdI Essentiality for Class Ib Ribonucleotide Reduction in Streptococcus pyogenes
Ignasi Roca; Eduard Torrents; Margareta Sahlin; Isidre Gibert; Britt-Marie Sjoberg
The Streptococcus pyogenes genome harbors two clusters of class Ib ribonucleotide reductase genes, nrdHEF and nrdF*I*E*, and a second stand-alone nrdI gene, designated nrdI2. We show that both clusters are expressed simultaneously as two independent operons. The NrdEF enzyme is functionally active in vitro, while the NrdE*F* enzyme is not. The NrdF* protein lacks three of the six highly conserved
[Monoarthritis caused by Streptococcus pyogenes after nasal septoplasty: interest of the nasal decontamination in preoperative care].
Gardes, S; Hellot, M; Tringali, S; Larbre, J-P; Biron, F; Llorca, G; Girard, R
The nasal septoplasty is a very current intervention in otorhinolaryngology surgery. The infectious complications of this intervention are rare and mostly mild. We report here the case of a patient hospitalized in ambulatory surgery within a fracture of the nose with luxation of the septum in the nasal fossa. This patient was operated for a reduction of this fracture with septoplasty. Twelve hours after the intervention the patient presented septic arthritis due to Streptococcus pyogenes. The tracks of prevention are presented. PMID:20018472
Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging
Alam, Faraz M.; Bateman, Colin; Turner, Claire E.; Wiles, Siouxsie; Sriskandan, Shiranee
Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 105 bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines. PMID:24278474
Inactivation of the Rgg2 Transcriptional Regulator Ablates the Virulence of Streptococcus pyogenes
Zutkis, Anastasia A.; Anbalagan, Srivishnupriya; Chaussee, Michael S.; Dmitriev, Alexander V.
Streptococcus pyogenes adapts to different niches encountered in the human host via the activity of numerous regulatory proteins including the Rgg family of transcriptional regulators. The S. pyogenes chromosome encodes four Rgg paralogues designated Rgg1 (RopB), Rgg2 (MutR), Rgg3, and Rgg4 (ComR). In order to understand the role of the Rgg2 protein in the regulation of metabolic and virulence-associated properties of S. pyogenes, the rgg2 gene was inactivated in the M1 serotype strain SF370. Inactivation of rgg2 increased the growth yield of S. pyogenes in THY broth, increased biofilm formation, and increased production of SIC, which is an important virulence factor that inhibits complement mediated lysis. To identify Rgg2-regulated genes, the transcriptomes of SF370 and the rgg2 mutant strains were compared in the middle-exponential and post-exponential phases of growth. Rgg2 was found to control the expression of dozens of genes primarily in the exponential phase of growth, including genes associated with virulence (sse, scpA, slo, nga, mf-3), DNA transformation, and nucleotide metabolism. Inactivation of rgg2 decreased the ability of S. pyogenes to adhere to epithelial cells. In addition, the mutant strain was more sensitive to killing when incubated with human blood and avirulent in a murine bacteremia model. Finally, inoculation of mice with the avirulent rgg2 mutant of S. pyogenes SF370 conferred complete protection to mice subsequently challenged with the wild-type strain. Restoration of an intact rgg2 gene in mutant strain restored the wild-type phenotypes. Overall, the results demonstrate that Rgg2 is an important regulatory protein in S. pyogenes involved in controlling genes associated with both metabolism and virulence. PMID:25486272
Antibacterial Activity of Rhodomyrtus tomentosa (Aiton) Hassk. Leaf Extract against Clinical Isolates of Streptococcus pyogenes
Limsuwan, Surasak; Kayser, Oliver; Voravuthikunchai, Supayang Piyawan
Ethanol extract of Rhodomyrtus tomentosa (Aiton) Hassk. leaf was evaluated for antibacterial activity against 47 clinical isolates of Streptococcus pyogenes. The extract exhibited good anti-S. pyogenes activity against all the tested isolates with similar minimum inhibitory concentration (MIC, 3.91–62.5??g?mL?1) and minimum bactericidal concentration (MBC, 3.91–62.5??g?mL?1) ranges. No surviving cells were detected at 16 h after treatment with 8?×?MIC of the extract. The extract-treated cells demonstrated no lysis and cytoplasmic leakage through the bacterial membrane. Electron micrographs further revealed that the extract did not cause any dramatic changes on the treated cells. Rhodomyrtone, an isolated compound, exhibited good anti-S. pyogenes activity (14 isolates), expressed very low MIC (0.39–1.56??g?mL?1) and MBC (0.39-1.56??g?mL?1) values. Rhodomyrtus tomentosa leaf extract and rhodomyrtone displayed promising antibacterial activity against clinical isolates of S. pyogenes. PMID:22973404
Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes
Patenge, Nadja; Pappesch, Roberto; Krawack, Franziska; Walda, Claudia; Mraheil, Mobarak Abu; Jacob, Anette; Hain, Torsten; Kreikemeyer, Bernd
While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs) specific for the essential gyrase A gene (gyrA). Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF)3K-coupled PNAs. Peptide-anti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function. PMID:24193033
The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from streptococcus pyogenes.
Chang, C.; Coggill, P.; Bateman, A.; Finn, R.; Cymborowski, M.; Otwinowski, Z.; Minor, W.; Volkart, L.; Joachimiak, A.; Wellcome Trust Sanger Inst.; Univ. of Virginia; UT Southwestern Medical Center
Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. We have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.
Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic acid bacteria.
Piard, J C; Hautefort, I; Fischetti, V A; Ehrlich, S D; Fons, M; Gruss, A
The M6 protein from Streptococcus pyogenes is the best-characterized member of a family of cell envelope-associated proteins. Based on the observation that the C-terminal sorting signals of these proteins can drive cell wall anchoring of heterologous unanchored proteins, we have cloned and expressed the emm6 structural gene for the M6 protein in various lactic acid bacteria (LAB). The emm6 gene was successfully expressed from lactococcal promoters in several Lactococcus lactis strains, an animal-colonizing Lactobacillus fermentum strain, Lactobacillus sake, and Streptococcus salivarius subsp. thermophilus. The M6 protein was efficiently anchored to the cell wall in all strains tested. In lactobacilli, essentially all detectable M6 protein was cell wall associated. These results suggest the feasibility of using the C-terminal anchor moiety of M6 for protein surface display in LAB. PMID:9139932
Overexpression and Enzymatic Assessment of Antigenic Fragments of Hyaluronidase Recombinant Protein From Streptococcus pyogenes
Sadoogh Abbasian, Shabnam; Ghaznavi Rad, Ehsanollah; Akbari, Neda; Zolfaghari, Mohammad Reza; pakzad, Iraj; Abtahi, Hamid
Background: Hyaluronidase catalyzes the hydrolysis of hyaluronan polymers to N-acetyl-D-glucosamine and D-glucuronic acid. This enzyme is a dimer of identical subunits. Hyaluronidase has different pharmaceutical and medical applications. Previously, we produced a recombinant hyaluronidase antigenic fragment of Streptococcus pyogenes. Objectives: This study aimed to improve the protein production and purity of hyaluronidase recombinant protein from S. pyogenes. In addition, the enzymatic activity of this protein was investigated. Materials and Methods: The expression of hyaluronidase antigenic fragments was optimized using IPTG concentration, time of induction, temperature, culture, and absorbance of 0.6-0.8-1 at 600 nm. Afterwards, the expressed proteins were purified and the enzymatic activity was assessed by turbid metric method. Results: Data indicated that maximum protein is produced in OD = 0.8, 0.5 mM Isopropyl ?-D-1-thiogalactopyranoside (IPTG), 37şC, NB 1.5x, without glucose, incubated for overnight. The enzymatic activity of the recombinant protein was similar to the commercial form of hyaluronidase. Conclusions: The results showed that an antigenic fragment of the recombinant hyaluronidase protein from S. pyogenes has a considerable enzymatic activity. It can be suggested to use it for medical purposes. In addition, applications of bioinformatics software would facilitate the production of a smaller protein with same antigenic properties and enzymatic activity. PMID:25789122
Characterization of hyaluronic acid specific hyaluronate lyase (HylP) from Streptococcus pyogenes.
Singh, Sudhir Kumar; Malhotra, Soniya; Akhtar, Md Sohail
Streptococcus pyogenes is associated with a wide variety of mucosal and invasive infections that claim human life. The conversion from non pathogenic to toxigenic strain of S. pyogenes are thought to be mediated by bacteriophage infection in several cases. The hyaluronic acid (HA) degrading enzyme Hyaluronate lyase (HL) is proposed to be one of the key bacteriophage-encoded virulence factors. In the present work, HL of S. pyogenes bacteriophage H4489A (HylP) was expressed in Escherichia coli, purified and their structural and functional properties were studied. The enzyme exists in an extended trimeric conformation whose function is influenced by calcium ions. The collagenous Gly-X-Y motif of the enzyme influences stability and interact with calcium ions suggesting its role in the enzyme regulation The HylP shows sequential unfolding through the N-terminal domain. The primary catalytic residues of the enzyme seem to be in the first pocket consisting of Asp170 and Tyr182; however the enzyme activity is considerably reduced with mutation in the second pocket consisting of Glu295 and Tyr298. The catalytic residues span between the regions containing 135-308 amino acids where both the catalytic pocket has a prominent positively charged residue. The net positive potential of the cleft may help in recruiting the negatively charged polymeric HA. Interestingly, unlike other phage HLs, HylP is inhibited by l-ascorbic through non competitive manner. PMID:24721581
Mode of Expression and Functional Characterization of FCT3 Pilus Region-Encoded Proteins in Streptococcus pyogenes Serotype M49
Masanobu Nakata; Thomas Koller; Karin Moritz; Deborah Ribardo; Ludwig Jonas; Kevin S. McIver; Tomoko Sumitomo; Yutaka Terao; Shigetada Kawabata; Andreas Podbielski; Bernd Kreikemeyer
The human pathogen Streptococcus pyogenes (group A streptococcus (GAS)) pilus components, suggested to play a role in pathogenesis, are encoded in the variable FCT (fibronectin- and collagen-binding T-antigen) region. We investigated the functions of sortase A (SrtA), sortase C2 (SrtC2), and the FctA protein of the most prevalent type 3 FCT region from a serotype M49 strain. Although it is
Plasmid-determined resistance to erythromycin: comparison of strains of streptococcus faecalis and streptococcus pyogenes with regard to plasmid hmology and resistance inducibility.
Yag, Y; Franke, A E; Clewell, D B
Streptococcus faecalis strains DS-5 and Streptococcus pyogenes strain AC-1 both have a 17 million dalton plasmid that determines resistance to erythromycin, lincomycin, and vernamycin B(alpha). The results of deoxyribonucleic acid-deoxyribonucleic acid hybridization experiments indicate that the two plasmids are about 95% homologous. It was also shown that erythromycin resistance is inducible in AC-1 and constitutive in DS-5. PMID:808161
Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation
Jason D. McArthur; Fiona C. McKay; Vidiya Ramachandran; Priya Shyam; Amanda J. Cork; Martina L. Sanderson-Smith; Jason N. Cole; Ulrika Ringdahl; Ulf Sjobring; Marie Ranson; Mark J. Walker
A common mammalian defense mecha- nism employed to prevent systemic dissemination of invasive bacteria involves occlusion of local microvas- culature and encapsulation of bacteria within fibrin networks. Acquisition of plasmin activity at the bacterial cell surface circumvents this defense mechanism, allow- ing invasive disease initiation. To facilitate this process, S. pyogenes secretes streptokinase, a plasminogen-acti- vating protein. Streptokinase polymorphism exhibited
Multilocus Sequence Typing of Streptococcus pyogenes Representing Most Known emm Types and Distinctions among Subpopulation Genetic Structures
Karen F. McGregor; Brian G. Spratt; Awdhesh Kalia; Alicia Bennett; Nicole Bilek; Bernard Beall; Debra E. Bessen
A long-term goal is to characterize the full range of genetic diversity within Streptococcus pyogenes as it exists in the world today. Since the emm locus is subject to strong diversifying selection, emm type was used as a guide for identifying a genetically diverse set of strains. This report contains a description of multilocus sequence typing based on seven housekeeping
Frequency of Spontaneous Resistance to Peptide Deformylase Inhibitor GSK1322322 in Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.
Min, Sharon; Ingraham, Karen; Huang, Jianzhong; McCloskey, Lynn; Rilling, Sarah; Windau, Anne; Pizzollo, Jason; Butler, Deborah; Aubart, Kelly; Miller, Linda A; Zalacain, Magdalena; Holmes, David J; O'Dwyer, Karen
The continuous emergence of multidrug-resistant pathogenic bacteria is compromising the successful treatment of serious microbial infections. GSK1322322, a novel peptide deformylase (PDF) inhibitor, shows good in vitro antibacterial activity and has demonstrated safety and efficacy in human proof-of-concept clinical studies. In vitro studies were performed to determine the frequency of resistance (FoR) to this antimicrobial agent in major pathogens that cause respiratory tract and skin infections. Resistance to GSK1322322 occurred at high frequency through loss-of-function mutations in the formyl-methionyl transferase (FMT) protein in Staphylococcus aureus (4/4 strains) and Streptococcus pyogenes (4/4 strains) and via missense mutations in Streptococcus pneumoniae (6/21 strains), but the mutations were associated with severe in vitro and/or in vivo fitness costs. The overall FoR to GSK1322322 was very low in Haemophilus influenzae, with only one PDF mutant being identified in one of four strains. No target-based mutants were identified from S. pyogenes, and only one or no PDF mutants were isolated in three of the four S. aureus strains studied. In S. pneumoniae, PDF mutants were isolated from only six of 21 strains tested; an additional 10 strains did not yield colonies on GSK1322322-containing plates. Most of the PDF mutants characterized from those three organisms (35/37 mutants) carried mutations in residues at or in close proximity to one of three highly conserved motifs that are part of the active site of the PDF protein, with 30 of the 35 mutations occurring at position V71 (using the S. pneumoniae numbering system). PMID:26014938
Structural Conservation, Variability, and Immunogenicity of the T6 Backbone Pilin of Serotype M6 Streptococcus pyogenes
Moreland, Nicole J.; Loh, Jacelyn M.; Bell, Anita; Atatoa Carr, Polly; Proft, Thomas; Baker, Edward N.
Group A streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection in vivo. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine. PMID:24778112
Functional and Structural Properties of a Novel Protein and Virulence Factor (Protein sHIP) in Streptococcus pyogenes *
Wisniewska, Magdalena; Happonen, Lotta; Kahn, Fredrik; Varjosalo, Markku; Malmström, Lars; Rosenberger, George; Karlsson, Christofer; Cazzamali, Giuseppe; Pozdnyakova, Irina; Frick, Inga-Maria; Björck, Lars; Streicher, Werner; Malmström, Johan; Wikström, Mats
Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment, enabling bacterial interactions with the host. In the present study, we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice with a non-virulent strain. Particularly, one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal histidine-rich glycoprotein-interacting protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP suggest a role for the protein in S. pyogenes pathogenesis. PMID:24825900
Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes.
Le Breton, Yoann; Belew, Ashton T; Valdes, Kayla M; Islam, Emrul; Curry, Patrick; Tettelin, Hervé; Shirtliff, Mark E; El-Sayed, Najib M; McIver, Kevin S
Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci. PMID:25996237
Rapid Development of Brain Abscess Caused by Streptococcus Pyogenes Following Penetrating Skull Injury via the Ethmoidal Sinus and Lamina Cribrosa
Aydin, Gerilmez; Cömert, Serhat; Altinors, Nur
Objective Streptococcus pyogenes is a beta-hemolytic bacterium that belongs to Lancefield serogroup A, also known as group A streptococci (GAS). There have been five reported case in terms of PubMed-based search but no reported case of brain abscess caused by Streptococcus pyogenes as a result of penetrating skull injury. We present a patient who suffered from penetrating skull injury that resulted in a brain abscess caused by Streptococcus pyogenes. Methods The patient was a 12-year-old boy who fell down from his bicycle while cycling and ran into a tree. A wooden stick penetrated his skin below the right lower eyelid and advanced to the cranium. He lost consciousness on the fifth day of the incident and his body temperature was measured as 40?. While being admitted to our hospital, a cranial computed tomography revealed a frontal cystic mass with a perilesional hypodense zone of edema. There was no capsule formation around the lesion after intravenous contrast injection. Paranasal CT showed a bone defect located between the ethmoidal sinus and lamina cribrosa. Results Bifrontal craniotomy was performed. The abscess located at the left frontal lobe was drained and the bone defect was repaired. Conclusion Any penetrating lesion showing a connection between the lamina cribrosa and ethmoidal sinus may result in brain abscess caused by Streptococcus pyogenes. These patients should be treated urgently to repair the defect and drain the abscess with appropriate antibiotic therapy started due to the fulminant course of the brain abscess caused by this microorganism. PMID:20717517
Iron-containing lipoprotein SiaA in SiaABC, the primary heme transporter of Streptococcus pyogenes
Xuesong Sun; Ruiguang Ge; Dongmei Zhang; Hongzhe Sun; Qing-Yu He
The cell-surface lipoprotein SiaA, a component of the SiaABC transporter, acts as the primary receptor for heme in the infamous\\u000a human pathogen Streptococcus pyogenes. However, little is known about the molecular mechanism of heme binding and release as well as the role of heme-binding ligands\\u000a that contribute to the uptake of heme into the pathogenic bacteria. The present report aims
M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes
Lisa I. Pahlman; Erik Malmstrom; Matthias Morgelin; Heiko Herwald
Invasive infections caused by the important pathogen Streptococcus pyogenes are often associated with disturbed blood coagulation in the human host, and may in severe cases develop into the life-threatening condition disseminated intravascular coagulation. In this study, the addition of M1 protein to human blood or purified peripheral blood mononuclear cells led to a dose-dependent increase of pro-coagulant activity, which was
Streptococcus pyogenes Pharyngeal Isolates with Reduced Susceptibility to Ciprofloxacin in Spain: Mechanisms of Resistance and Clonal Diversity
Albertí, Sebastián; Cortés, Guadalupe; García-Rey, Cesar; Rubio, Carmen; Baquero, Fernando; García-Rodríguez, José Ángel; Bouza, Emilio; Aguilar, Lorenzo
A survey of emm gene sequences and an analysis of the pulsed-field electrophoretic profiles of 30 Streptococcus pyogenes isolates with reduced susceptibilities to ciprofloxacin detected the prevalence of isolates with emm type 6 and considerable genetic diversity among isolates. The mechanism of ciprofloxacin resistance in these isolates was based on point mutations in topoisomerase IV subunit C encoded by parC, mainly replacement of serine-79 by alanine. PMID:15616324
A Novel Sortase, SrtC2, from Streptococcus pyogenes Anchors a Surface Protein Containing a QVPTGV Motif to the Cell Wall
Timothy C. Barnett; Aman R. Patel; June R. Scott
The important human pathogen Streptococcus pyogenes (group A streptococcus GAS), requires several surface proteins to interact with its human host. Many of these are covalently linked by a sortase enzyme to the cell wall via a C-terminal LPXTG motif. This motif is followed by a hydrophobic region and charged C terminus, which are thought to retard the protein in the
Molecular characterization of macrolide resistant Streptococcus pyogenes isolates from pharyngitis patients in Serbia.
Opavski, Natasa; Gajic, Ina; Borek, Anna L; Obsza?ska, Katarzyna; Stanojevic, Maja; Lazarevic, Ivana; Ranin, Lazar; Sitkiewicz, Izabela; Mijac, Vera
A steady increase in macrolide resistance in Streptococcus pyogenes, group A streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS (MRGAS) isolates. Therefore, the aims of this first nationwide study were to examine the prevalence of macrolide resistance in Serbian GAS and to determine their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non-duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection were collected throughout country during 2008 and 2009. Among 486 macrolide resistant pharyngeal isolates collected, 103 were further characterized. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion test and PCR, respectively. Strain relatedness was determined by emm typing, multilocus sequence typing (MLST), multilocus variable tandem repeat analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP). Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three clonal complexes - emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63 comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished 10, 20 and 12 different patterns, respectively, cluster analysis disclosed only small differences between strains which belonged to the same emm/ST type. Our data indicate dominance of three major internationally widely disseminated macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS population. Continued surveillance of macrolide resistance and clonal composition in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones and to guide therapy strategies. PMID:25976381
Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements
Falaleeva, Marina; Zurek, Oliwia W.; Watkins, Robert L.; Reed, Robert W.; Ali, Hadeel; Sumby, Paul; Voyich, Jovanka M.
The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence. PMID:25287924
Identification and Characterization of Two Temperature-Induced Surface-Associated Proteins of Streptococcus suis with High Homologies to Members of the Arginine Deiminase System of Streptococcus pyogenes
Winterhoff, Nora; Goethe, Ralph; Gruening, Petra; Rohde, Manfred; Kalisz, Henryk; Smith, Hilde E.; Valentin-Weigand, Peter
The present study was performed to identify stress-induced putative virulence proteins of Streptococcus suis. For this, protein expression patterns of streptococci grown at 32, 37, and 42°C were compared by one- and two-dimensional gel electrophoresis. Temperature shifts from 32 and 37 to 42°C induced expression of two cell wall-associated proteins with apparent molecular masses of approximately 47 and 53 kDa. Amino-terminal sequence analysis of the two proteins indicated homologies of the 47-kDa protein with an ornithine carbamoyltransferase (OCT) from Streptococcus pyogenes and of the 53-kDa protein with the streptococcal acid glycoprotein (SAGP) from S. pyogenes, an arginine deiminase (AD) recently proposed as a putative virulence factor. Cloning and sequencing the genes encoding the putative OCT and AD of S. suis, octS and adiS, respectively, revealed that they had 81.2 (octS) and 80.2% (adiS) identity with the respective genes of S. pyogenes. Both genes belong to the AD system, also found in other bacteria. Southern hybridization analysis demonstrated the presence of the adiS gene in all 42 serotype 2 and 9 S. suis strains tested. In 9 of these 42 strains, selected randomly, we confirmed expression of the AdiS protein, homologous to SAGP, by immunoblot analysis using a specific antiserum against the SAGP of S. pyogenes. In all strains AD activity was detected. Furthermore, by immunoelectron microscopy using the anti-S. pyogenes SAGP antiserum we were able to demonstrate that the AdiS protein is expressed on the streptococcal surface in association with the capsular polysaccharides but is not coexpressed with them. PMID:12446626
Identification and characterization of two temperature-induced surface-associated proteins of Streptococcus suis with high homologies to members of the Arginine Deiminase system of Streptococcus pyogenes.
Winterhoff, Nora; Goethe, Ralph; Gruening, Petra; Rohde, Manfred; Kalisz, Henryk; Smith, Hilde E; Valentin-Weigand, Peter
The present study was performed to identify stress-induced putative virulence proteins of Streptococcus suis. For this, protein expression patterns of streptococci grown at 32, 37, and 42 degrees C were compared by one- and two-dimensional gel electrophoresis. Temperature shifts from 32 and 37 to 42 degrees C induced expression of two cell wall-associated proteins with apparent molecular masses of approximately 47 and 53 kDa. Amino-terminal sequence analysis of the two proteins indicated homologies of the 47-kDa protein with an ornithine carbamoyltransferase (OCT) from Streptococcus pyogenes and of the 53-kDa protein with the streptococcal acid glycoprotein (SAGP) from S. pyogenes, an arginine deiminase (AD) recently proposed as a putative virulence factor. Cloning and sequencing the genes encoding the putative OCT and AD of S. suis, octS and adiS, respectively, revealed that they had 81.2 (octS) and 80.2% (adiS) identity with the respective genes of S. pyogenes. Both genes belong to the AD system, also found in other bacteria. Southern hybridization analysis demonstrated the presence of the adiS gene in all 42 serotype 2 and 9 S. suis strains tested. In 9 of these 42 strains, selected randomly, we confirmed expression of the AdiS protein, homologous to SAGP, by immunoblot analysis using a specific antiserum against the SAGP of S. pyogenes. In all strains AD activity was detected. Furthermore, by immunoelectron microscopy using the anti-S. pyogenes SAGP antiserum we were able to demonstrate that the AdiS protein is expressed on the streptococcal surface in association with the capsular polysaccharides but is not coexpressed with them. PMID:12446626
Differential Recognition of Surface Proteins in Streptococcus pyogenes by Two Sortase Gene Homologs
Barnett, Timothy C.; Scott, June R.
The interaction of Streptococcus pyogenes (group A streptococcus [GAS]) with its human host requires several surface proteins. In this study, we isolated mutations in a gene required for the surface localization of protein F by transposon mutagenesis of the M6 strain JRS4. This gene (srtA) encodes a protein homologous to Staphylococcus aureus sortase, which covalently links proteins containing an LPXTG motif to the cell wall. The GAS srtA mutant was defective in anchoring the LPXTG-containing proteins M6, protein F, ScpA, and GRAB to the cell surface. This phenotype was complemented when a wild-type srtA gene was provided in trans. The surface localization of T6, however, was unaffected by the srtA mutation. The M1 genome sequence contains a second open reading frame with a motif characteristic of sortase proteins. Inactivation of this gene (designated srtB) in strain JRS4 affected the surface localization of T6 but not M6, protein F, ScpA, or GRAB. This phenotype was complemented by srtB in trans. An srtA probe hybridized with DNA from all GAS strains tested (M types 1, 3, 4, 5, 6, 18, 22, and 50 and nontypeable strain 64/14) and from streptococcal groups C and G, while srtB hybridized with DNA from only a few GAS strains. We conclude that srtA and srtB encode sortase enzymes required for anchoring different subsets of proteins to the cell wall. It seems likely that the multiple sortase homologs in the genomes of other gram-positive bacteria have a similar substrate-specific role. PMID:11914350
Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes
Soares, Elyara M.; Mason, Katie L.; Rogers, Lisa M.; Serezani, Carlos H.; Faccioli, Lucia H.; Aronoff, David M.
Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes (Group A Streptococcus; GAS) is a major etiologic agent of severe postpartum sepsis yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B4 has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB4 to modulate anti-streptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase (5LO) enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5LO were significantly more vulnerable to intrauterine GAS infection than wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response compared to wild-type mice. Additionally, LTB4 reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase-dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB4 and the cAMP-inducing lipid prostaglandin E2, suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections. PMID:23325886
Cellular aspects of M protein and SfbI anchoring to Streptococcus pyogenes wall
Raz, Assaf; Talay, Susanne; Fischetti, Vincent
Summary Wall-anchored surface proteins are critical for the in vivo survival of Streptococcus pyogenes. Cues in the signal sequence direct the membrane translocation of surface proteins: M protein to the septum, and SfbI to the poles. Both proteins are subsequently anchored to the wall by the membrane bound enzyme sortase A. However, the cellular features of these pathways are not fully understood. Here we show that M protein and SfbI are anchored simultaneously throughout the cell cycle. M protein is rapidly anchored at the septum, and in part of the cell cycle, is anchored simultaneously at the mother and daughter septa. Conversely, SfbI accumulates gradually on peripheral peptidoglycan, resulting in a polar distribution. Sortase is not required for translocation of M protein or SfbI at their respective locations. Methicillin-induced unbalanced peptidoglycan synthesis diminishes surface M protein but not SfbI. Furthermore, overexpression of the division regulator DivIVA also diminishes surface M protein but increases SfbI. These results demonstrate a close connection between the regulation of cell division and protein anchoring. Better understanding of the spatial regulation of surface anchoring may lead to the identification of novel targets for the development of anti-infective agents, given the importance of surface molecules for pathogenesis. PMID:22512736
Structural Studies of Streptococcus pyogenes Streptolysin O Provide Insights into the Early Steps of Membrane Penetration
Feil, Susanne C.; Ascher, David B.; Kuiper, Michael J.; Tweten, Rodney K.; Parker, Michael W.
Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins that exhibit a dependence on the presence of membrane cholesterol in forming large pores in cell membranes. Significant changes in the three-dimensional structure of these toxins are necessary to convert the soluble monomeric protein into a membrane pore. We have determined the crystal structure of the archetypical member of the CDC family, streptolysin O (SLO), a virulence factor from Streptococcus pyogenes. The overall fold is similar to previously reported CDC structures, although the C-terminal domain is in a different orientation with respect to the rest of the molecule. Surprisingly, a signature stretch of CDC sequence called the undecapeptide motif, a key region involved in membrane recognition, adopts a very different structure in SLO to that of the well-characterized CDC perfringolysin O (PFO), although the sequences in this region are identical. An analysis reveals that, in PFO, there are complementary interactions between the motif and the rest of domain 4 that are lost in SLO. Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and a cation–pi interaction are determining factors in the extended conformation of the motif, which in turn appears to result in a greater flexibility of the neighboring L1 loop that houses a cholesterol-sensing motif. These differences may explain the differing abilities of SLO and PFO to efficiently penetrate target cell membranes in the first step of toxin insertion into the membrane. PMID:24316049
Molecular modeling and simulation of FabG, an enzyme involved in the fatty acid pathway of Streptococcus pyogenes.
Shafreen, Rajamohmed Beema; Pandian, Shunmugiah Karutha
Streptococcus pyogenes (SP) is the major cause of pharyngitis accompanied by strep throat infections in humans. 3-keto acyl reductase (FabG), an important enzyme involved in the elongation cycle of the fatty acid pathway of S. pyogenes, is essential for synthesis of the cell-membrane, virulence factors and quorum sensing-related mechanisms. Targeting SPFabG may provide an important aid for the development of drugs against S. pyogenes. However, the absence of a crystal structure for FabG of S. pyogenes limits the development of structure-based drug designs. Hence, in the present study, a homology model of FabG was generated using the X-ray crystallographic structure of Aquifex aeolicus (PDB ID: 2PNF). The modeled structure was refined using energy minimization. Furthermore, active sites were predicted, and a large dataset of compounds was screened against SPFabG. The ligands were docked using the LigandFit module that is available from Discovery Studio version 2.5. From this list, 13 best hit ligands were chosen based on the docking score and binding energy. All of the 13 ligands were screened for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties. From this, the two best descriptors, along with one descriptor that lay outside the ADMET plot, were selected for molecular dynamic (MD) simulation. In vitro testing of the ligands using biological assays further substantiated the efficacy of the ligands that were screened based on the in silico methods. PMID:23988477
Single- and Multistep Resistance Selection Studies on the Activity of Retapamulin Compared to Other Agents against Staphylococcus aureus and Streptococcus pyogenes
Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C.
Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus. PMID:16436741
Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells
Ville Veckman; Minja Miettinen; Jaana Pirhonen; Jukka Siren; Sampsa Matikainen; Ilkka Julkunen
Dendritic cells (DCs) are the most ef- ficient antigen-presenting cells and thus, have a major role in regulating host immune responses. In the present study, we have analyzed the ability of Gram-positive, pathogenic Streptococcus pyogenes and nonpathogenic Lactobacillus rhamnosus to in- duce the maturation of human monocyte-derived DCs. Stimulation of DCs with S. pyogenes resulted in strong expression of DC
Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation
Baldassarri, Lucilla; Creti, Roberta; Recchia, Simona; Imperi, Monica; Facinelli, Bruna; Giovanetti, Eleonora; Pataracchia, Marco; Alfarone, Giovanna; Orefici, Graziella
Streptococcus pyogenes infections often fail to respond to antibiotic therapy, leading to persistent throat carriage and recurrent infections. Such failures cannot always be explained by the occurrence of antibiotic resistance determinants, and it has been suggested that S. pyogenes may enter epithelial cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains isolated from different clinical sources to evaluate their ability to form biofilm as an alternative method to escape antibiotic treatment and host defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive infections, were able to form biofilm. Specific emm types, such as emm6, appeared to be more likely to produce biofilm, although variations within strains belonging to the same type might suggest biofilm formation to be a trait of individual strains rather than a general attribute of a serotype. Interestingly, erythromycin-susceptible isolates formed a significantly thicker biofilm than resistant isolates (P < 0.05). Among resistant strains, those carrying the erm class determinants formed a less organized biofilm than the mef(A)-positive strains. Also, prtF1 appeared to be negatively associated with the ability to form biofilm (P < 0.01). Preliminary data on a selection of strains indicated that biofilm-forming isolates entered epithelial cells with significantly lower efficiency than biofilm-negative strains. We suggest that prtF1-negative macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to enter cells, may use biofilm to escape antimicrobial treatments and survive within the host. In this view, biofilm formation by S. pyogenes could be responsible for unexplained treatment failures and recurrences due to susceptible microorganisms. PMID:16891483
Therapeutic failures of antibiotics used to treat macrolide-susceptible Streptococcus pyogenes infections may be due to biofilm formation.
Baldassarri, Lucilla; Creti, Roberta; Recchia, Simona; Imperi, Monica; Facinelli, Bruna; Giovanetti, Eleonora; Pataracchia, Marco; Alfarone, Giovanna; Orefici, Graziella
Streptococcus pyogenes infections often fail to respond to antibiotic therapy, leading to persistent throat carriage and recurrent infections. Such failures cannot always be explained by the occurrence of antibiotic resistance determinants, and it has been suggested that S. pyogenes may enter epithelial cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains isolated from different clinical sources to evaluate their ability to form biofilm as an alternative method to escape antibiotic treatment and host defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive infections, were able to form biofilm. Specific emm types, such as emm6, appeared to be more likely to produce biofilm, although variations within strains belonging to the same type might suggest biofilm formation to be a trait of individual strains rather than a general attribute of a serotype. Interestingly, erythromycin-susceptible isolates formed a significantly thicker biofilm than resistant isolates (P < 0.05). Among resistant strains, those carrying the erm class determinants formed a less organized biofilm than the mef(A)-positive strains. Also, prtF1 appeared to be negatively associated with the ability to form biofilm (P < 0.01). Preliminary data on a selection of strains indicated that biofilm-forming isolates entered epithelial cells with significantly lower efficiency than biofilm-negative strains. We suggest that prtF1-negative macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to enter cells, may use biofilm to escape antimicrobial treatments and survive within the host. In this view, biofilm formation by S. pyogenes could be responsible for unexplained treatment failures and recurrences due to susceptible microorganisms. PMID:16891483
Assembly Mechanism of FCT Region Type 1 Pili in Serotype M6 Streptococcus pyogenes*
Nakata, Masanobu; Kimura, Keiji Richard; Sumitomo, Tomoko; Wada, Satoshi; Sugauchi, Akinari; Oiki, Eiji; Higashino, Miharu; Kreikemeyer, Bernd; Podbielski, Andreas; Okahashi, Nobuo; Hamada, Shigeyuki; Isoda, Ryutaro; Terao, Yutaka; Kawabata, Shigetada
The human pathogen Streptococcus pyogenes produces diverse pili depending on the serotype. We investigated the assembly mechanism of FCT type 1 pili in a serotype M6 strain. The pili were found to be assembled from two precursor proteins, the backbone protein T6 and ancillary protein FctX, and anchored to the cell wall in a manner that requires both a housekeeping sortase enzyme (SrtA) and pilus-associated sortase enzyme (SrtB). SrtB is primarily required for efficient formation of the T6 and FctX complex and subsequent polymerization of T6, whereas proper anchoring of the pili to the cell wall is mainly mediated by SrtA. Because motifs essential for polymerization of pilus backbone proteins in other Gram-positive bacteria are not present in T6, we sought to identify the functional residues involved in this process. Our results showed that T6 encompasses the novel VAKS pilin motif conserved in streptococcal T6 homologues and that the lysine residue (Lys-175) within the motif and cell wall sorting signal of T6 are prerequisites for isopeptide linkage of T6 molecules. Because Lys-175 and the cell wall sorting signal of FctX are indispensable for substantial incorporation of FctX into the T6 pilus shaft, FctX is suggested to be located at the pilus tip, which was also implied by immunogold electron microscopy findings. Thus, the elaborate assembly of FCT type 1 pili is potentially organized by sortase-mediated cross-linking between sorting signals and the amino group of Lys-175 positioned in the VAKS motif of T6, thereby displaying T6 and FctX in a temporospatial manner. PMID:21880740
Adaptive Evolution of the Streptococcus pyogenes Regulatory Aldolase LacD.1
Cusumano, Zachary
In the human-pathogenic bacterium Streptococcus pyogenes, the tagatose bisphosphate aldolase LacD.1 likely originated through a gene duplication event and was adapted to a role as a metabolic sensor for regulation of virulence gene transcription. Although LacD.1 retains enzymatic activity, its ancestral metabolic function resides in the LacD.2 aldolase, which is required for the catabolism of galactose. In this study, we compared these paralogous proteins to identify characteristics correlated with divergence and novel function. Surprisingly, despite the fact that these proteins have identical active sites and 82% similarity in amino acid sequence, LacD.1 was less efficient at cleaving both fructose and tagatose bisphosphates. Analysis of kinetic properties revealed that LacD.1's adaptation was associated with a decrease in kcat and an increase in Km. Construction and analysis of enzyme chimeras indicated that non-active-site residues previously associated with the variable activities of human aldolase isoenzymes modulated LacD.1's affinity for substrate. Mutant LacD.1 proteins engineered to have LacD.2-like levels of enzymatic efficiency lost the ability to function as regulators, suggesting that an alteration in efficiency was required for adaptation. In competition under growth conditions that mimic a deep-tissue environment, LacD.1 conferred a significant gain in fitness that was associated with its regulatory activity. Taken together, these data suggest that LacD.1's adaptation represents a form of neofunctionalization in which duplication facilitated the gain of regulatory function important for growth in tissue and pathogenesis. PMID:23316044
Protective Mechanisms of Respiratory Tract Streptococci against Streptococcus pyogenes Biofilm Formation and Epithelial Cell Infection
Fiedler, Tomas; Riani, Catur; Koczan, Dirk; Standar, Kerstin
Streptococcus pyogenes (group A streptococci [GAS]) encounter many streptococcal species of the physiological microbial biome when entering the upper respiratory tract of humans, leading to the question how GAS interact with these bacteria in order to establish themselves at this anatomic site and initiate infection. Here we show that S. oralis and S. salivarius in direct contact assays inhibit growth of GAS in a strain-specific manner and that S. salivarius, most likely via bacteriocin secretion, also exerts this effect in transwell experiments. Utilizing scanning electron microscopy documentation, we identified the tested strains as potent biofilm producers except for GAS M49. In mixed-species biofilms, S. salivarius dominated the GAS strains, while S. oralis acted as initial colonizer, building the bottom layer in mixed biofilms and thereby allowing even GAS M49 to form substantial biofilms on top. With the exception of S. oralis, artificial saliva reduced single-species biofilms and allowed GAS to dominate in mixed biofilms, although the overall two-layer structure was unchanged. When covered by S. oralis and S. salivarius biofilms, epithelial cells were protected from GAS adherence, internalization, and cytotoxic effects. Apparently, these species can have probiotic effects. The use of Affymetrix array technology to assess HEp-2 cell transcription levels revealed modest changes after exposure to S. oralis and S. salivarius biofilms which could explain some of the protective effects against GAS attack. In summary, our study revealed a protection effect of respiratory tract bacteria against an important airway pathogen and allowed a first in vitro insight into local environmental processes after GAS enter the respiratory tract. PMID:23241973
Incidental detection of S. pyogenes DNA in psoriatic skin by PCR
P. Weisenseel; J. C. Prinz
Psoriasis vulgaris is a T cell-mediated autoimmune skin disease. First disease onset and disease worsening are often triggered by tonsillar infection with Streptococcus pyogenes. Here we demonstrate the incidental detection of S. pyogenes DNA in samples of different biological origin from patients with chronic plaque-type psoriasis by PCR. These findings may support the model of molecular mimicry in psoriasis pathogenesis.
Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells.
Talay, S R; Valentin-Weigand, P; Jerlström, P G; Timmis, K N; Chhatwal, G S
The sequence of the fibronectin-binding domain of the fibronectin-binding protein of Streptococcus pyogenes (Sfb protein) was determined, and its role in streptococcal adherence was investigated by use of an Sfb fusion protein in adherence studies. A 1-kb DNA fragment coding for the binding domain of Sfb protein was cloned into the expression vector pEX31 to produce an Sfb fusion protein consisting of the N-terminal part of MS2 polymerase and a C-terminal fragment of the streptococcal protein. Induction of the vector promoter resulted in hyperexpression of fibronectin-binding fusion protein in the cytoplasm of the recombinant Escherichia coli cells. Sequence determination of the cloned 1-kb fragment revealed an in-frame reading frame for a 268-amino-acid peptide composed of a 37-amino-acid sequence which is completely repeated three times and incompletely repeated a fourth time. Cloning of one repeat into pEX31 resulted in expression of small fusion peptides that show fibronectin-binding activity, indicating that one repeat contains at least one binding domain. Each repeat exhibits two charged domains and shows high homology with the 38-amino-acid D3 repeat of the fibronectin-binding protein of Staphylococcus aureus. Sequence comparison with other streptococcal ligand-binding surface proteins, including M protein, failed to reveal significant homology, which suggests that Sfb protein represents a novel type of functional protein in S. pyogenes. The Sfb fusion protein isolated from the cytoplasm of recombinant cells was purified by fast protein liquid chromatography. It showed a strong competitive inhibition of fibronectin binding to S. pyogenes and of the adherence of bacteria to cultured epithelial cells. In contrast, purified streptococcal lipoteichoic acid showed only a weak inhibition of fibronectin binding and streptococcal adherence. These results demonstrate that Sfb protein is directly involved in the fibronectin-mediated adherence of S. pyogenes to epithelial cells. Images PMID:1386839
Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus
Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor
SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436
A new selective blood agar medium for Streptococcus pyogenes and other haemolytic streptococci
E. J. L. Lowbury; A. Kidson; H. A. Lilly
Horse blood agar containing polymyxin B sulphate, neomycin sulphate, and fusidic acid inhibited the growth of Staph. aureus, Ps. pyocyanea, Proteus mirabilis, E. coli, and Klebsiella pneumoniae but allowed good growth of, and haemolysis by, Str. pyogenes.In a comparison with blood agar, blood 4% agar, and gentian violet blood agar, the selective medium (P.N.F.) yielded a significantly higher proportion of
Comparison of rhesus and cynomolgus macaques in a Streptococcus pyogenes infection model for vaccine evaluation.
Skinner, Julie M; Caro-Aguilar, Ivette C; Payne, Angela M; Indrawati, Lani; Fontenot, Jane; Heinrichs, Jon H
Animal models predictive of human disease are generally difficult to establish and reproduce. In the case of the Group A Streptococcus (GAS) bacterium, which is predominantly a human pathogen, virulence assessment in animal models is problematic. We compared a monkey colonization and pharyngitis model of infection in two macaque species to determine the optimal model for vaccine candidate evaluation. Rhesus and cynomolgus macaques were intranasally infected with a streptomycin resistant (Str(r)) GAS strain. Monkeys were monitored for body weight and temperature changes, throat swabs and sera were collected, and clinical observations were noted throughout the study. Both species exhibited oropharyngeal colonization by GAS, with rhesus macaques demonstrating a more sustained colonization through day 28 post-challenge. Veterinary observations revealed no significant differences between GAS-infected rhesus and cynomolgus macaques. Mock-infected monkeys did not exhibit clinical symptoms or GAS colonization throughout the study. ELISA results demonstrated that both rhesus and cynomolgus macaques developed anti-streptolysin-O antibody titers, with cynomolgus generating higher titers. Sera from infected monkeys produced opsonophagocytic killing and bound to the bacterium in an immunofluorescence assay. Both rhesus and cynomolgus macaques can be used for colonization studies with this GAS M3 strain, yet only mild clinical signs of pharyngitis and tonsillitis were observed. PMID:21035535
A Two-Component Regulatory System, CsrR-CsrS, Represses Expression of Three Streptococcus pyogenes Virulence Factors, Hyaluronic Acid Capsule, Streptolysin S, and Pyrogenic Exotoxin B
Certain Tn916 insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenes isolate (MGAS166) were previously shown to result in stable mucoidy with increased expression of the capsular synthetic genes. The transposon insertions in these strains are directly upstream of an apparent operon encoding a two-component regulatory system, designated csrR-csrS. Compared with MGAS166, these mucoid mutants are more hemolytic and
Complete Genome Sequence of Streptococcus pyogenes M/emm44 Strain STAB901, Isolated in a Clonal Outbreak in French Brittany
Soriano, Nicolas; Vincent, Pascal; Piau, Caroline; Moullec, Séverine; Gautier, Philippe; Lagente, Vincent
We report the complete genome sequence of an invasive isolate of Streptococcus pyogenes M/emm44, belonging to a clonal outbreak that occurred in French Brittany. The genome is composed of 1,795,608 bp, with a GC content of 38.5%, has 1,358 identified coding sequences (CDSs), and harbors a novel Tn916-like transposon (Tn6253). PMID:25414498
Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation.
Aggarwal, Chaitanya; Jimenez, Juan Cristobal; Nanavati, Dhaval; Federle, Michael J
Streptococcus pyogenes, a human-restricted pathogen, accounts for substantial mortality related to infections worldwide. Recent studies indicate that streptococci produce and respond to several secreted peptide signaling molecules (pheromones), including those known as short hydrophobic peptides (SHPs), to regulate gene expression by a quorum-sensing mechanism. Upon transport into the bacterial cell, pheromones bind to and modulate activity of receptor proteins belonging to the Rgg family of transcription factors. Previously, we reported biofilm regulation by the Rgg2/3 quorum-sensing circuit in S. pyogenes. The aim of this study was to identify the composition of mature pheromones from cell-free culture supernatants that facilitate biofilm formation. Bioluminescent reporters were employed to detect active pheromones in culture supernatants fractionated by reverse-phase chromatography, and mass spectrometry was used to characterize their properties. Surprisingly, multiple SHPs that varied by length were detected. Synthetic peptides of each variant were tested individually using bioluminescence reporters and biofilm growth assays, and although activities differed widely among the group, peptides comprising the C-terminal eight amino acids of the full-length native peptide were most active. Direct Rgg/SHP interactions were determined using a fluorescence polarization assay that utilized FITC-labeled peptide ligands. Peptide receptor affinities were seen to be as low as 500 nm and their binding affinities directly correlated with observed bioactivity. Revelation of naturally produced pheromones along with determination of their affinity for cognate receptors are important steps forward in designing compounds whose purpose is positioned for future therapeutics aimed at treating infections through the interference of bacterial communication. PMID:24958729
Constitutive expression of fibronectin binding in Streptococcus pyogenes as a result of anaerobic activation of rofA.
Fogg, G C; Caparon, M G
Protein F is a fibronectin-binding surface protein of Streptococcus pyogenes (group A streptococcus) that mediates adherence to host cells. A gene product encoded by rofA activates transcription of the gene that encodes protein F (prtF) and was identified in a strain of S. pyogenes that expressed high levels of protein F under all conditions tested. Insertional inactivation of rofA in this strain results in a phenotype similar to that of other strains where high-level transcription of prtF occurs only in response to increased oxygen tension. In this study, we have compared the regulation of prtF and rofA in O2-regulated and constitutive strains in order to gain further insight into the function of rofA. Comparison of the prtF and rofA transcripts by S1 nuclease and primer extension assays indicated that the same promoters for each transcript are used in both O2-regulated and constitutive strains. However, analyses of rofA-lacZ reporter alleles revealed that a key difference between strains involves regulation of rofA itself. In O2-regulated strains, expression of rofA was elevated following culture under conditions of reduced O2 tension. However, a much more robust activation of rofA expression was observed when constitutive strains were grown under similar conditions. Exchange of reporter and rofA alleles between strains demonstrated that host genetic background, and not the sequence of the respective rofA allele or regulatory region, dictates the expression phenotype. Activation of rofA required RofA, and RofA was shown to bind specifically to DNA containing the promoters for rofA and prtF. Finally, overexpression of either allele of rofA caused constitutive expression of prtF regardless of host background. These data suggest a model where anaerobic expression of prtF in constitutive hosts is controlled at the level of transcription of rofA and implicate additional factors in this regulatory pathway. PMID:9324268
A role for trigger factor and an rgg-like regulator in the transcription, secretion and processing of the cysteine proteinase of Streptococcus pyogenes.
Lyon, W R; Gibson, C M; Caparon, M G
The ability of numerous microorganisms to cause disease relies upon the highly regulated expression of secreted proteinases. In this study, mutagenesis with a novel derivative of Tn4001 was used to identify genes required for the expression of the secreted cysteine proteinase (SCP) of the pathogenic Gram-positive bacterium Streptococcus pyogenes. Designated as Rop loci (regulation of proteinase), ropB is a rgg-like transcriptional activator required for transcription of the gene which encodes the proteinase. In contrast, ropA contributes post-transcriptionally to the secretion and processing of SCP and encodes a homologue of Trigger Factor, a peptidyl-prolyl isomerase and putative chaparone which is highly conserved in most bacterial species, but of unknown function. Analysis of additional ropA mutants demonstrated that RopA acts both to assist in targeting SCP to the secretory pathway and to promote the ability of the proprotein to establish an active conformation upon secretion. This latter function was dependent upon the peptidyl-prolyl isomerase domain of RopA and mutants that lacked this domain exhibited a bipartite deficiency manifested as a kinetic defect in autologous processing of the proprotein to the mature proteinase, and as a catalytic defect in the mature proteinase. These results provide insight into the function of Trigger Factor, the regulation of proteinase activity and the mechanism of secretion in Gram-positive bacteria. PMID:9799235
Antimicrobial Susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes Isolates and Their Ecological Relationships: Results of a 1-Year (1998–1999) Multicenter Surveillance Study in Spain
Pérez-Trallero, E.; Fernández-Mazarrasa, C.; García-Rey, C.; Bouza, E.; Aguilar, L.; García-de-Lomas, J.; Baquero, F.
A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was ?4 ?g/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, ?4 ?g/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae. PMID:11709305
Insertional inactivation of Streptococcus pyogenes sod suggests that prtF is regulated in response to a superoxide signal.
Gibson, C M; Caparon, M G
In establishing an infection, Streptococcus pyogenes has the capacity to bind to the host extracellular matrix protein fibronectin via its protein F adhesin. Previous studies have suggested that the expression of protein F is stimulated during aerobic growth or upon addition of superoxide-generating agents to the culture under O2-limited conditions. To further explore the role of superoxide, we have examined the transcription of the gene which encodes protein F (prtF), as well as the expression of superoxide dismutase (SOD) under conditions which promote or repress protein F expression. These studies show that prtF transcription is regulated in response to superoxide concentration and that SOD is regulated in different environments in a manner which directly parallels the expression of protein F. A mutant deficient in SOD activity was constructed by insertional mutation into the gene which encodes SOD (sod). The resulting mutant was sensitive to superoxide and aerobic conditions, showed hypersensitive induction of prtF in response to superoxide, and expressed prtF under normally unfavorable O2-limited conditions. These findings suggest that a streptococcal signal transduction system which senses superoxide may coordinately control expression of prtF and sod. PMID:8755901
TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes.
Eigenbrod, Tatjana; Pelka, Karin; Latz, Eicke; Kreikemeyer, Bernd; Dalpke, Alexander H
Microbial nucleic acids constitute an important group of pathogen-associated molecular patterns (PAMPs) that efficiently trigger innate immune activation. In mice, TLR13 has recently been identified to sense a highly conserved region within bacterial 23S rRNA. However, TLR13 is not expressed in humans, and the identity of its human homolog remains elusive. Moreover, the contribution of bacterial RNA to the induction of innate immune responses against entire bacteria is still insufficiently defined. In the current study, we show that human monocytes respond to bacterial RNA with secretion of IL-6, TNF, and IFN-?, which is critically dependent on lysosomal maturation. Using small interfering RNA and overexpression, we unambiguously identify TLR8 as receptor for bacterial RNA in primary human monocyte-derived macrophages. We further demonstrate that the sequence motif sensed by TLR8 is clearly distinct from that recognized by TLR13. Moreover, TLR8-dependent detection of bacterial RNA was critical for triggering monocyte activation in response to infection with Streptococcus pyogenes. Bacterial RNA within streptococci was also a dominant stimulus for murine immune cells, highlighting the physiological relevance of RNA sensing in defense of infections. PMID:26101323
Structural insight into the substrate inhibition mechanism of NADP(+)-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes.
Jang, Eun Hyuk; Park, Seong Ah; Chi, Young Min; Lee, Ki Seog
Succinic semialdehyde dehydrogenases (SSADHs) are ubiquitous enzymes that catalyze the oxidation of succinic semialdehyde (SSA) to succinic acid in the presence of NAD(P)(+), and play an important role in the cellular mechanisms including the detoxification of accumulated SSA or the survival in conditions of limited nutrients. Here, we report the inhibitory properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) in a binary (ES) complex with SSA as the substrate and a ternary (ESS) complex with the substrate SSA and the inhibitory SSA, at 2.4 Ĺ resolution for both structures. Analysis of the kinetic inhibitory parameters revealed significant substrate inhibition in the presence of NADP(+) at concentrations of SSA higher than 0.02 mM, which exhibited complete uncompetitive substrate inhibition with the inhibition constant (Ki) value of 0.10 ± 0.02 mM. In ES-complex of SpSSADH, the SSA showed a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Moreover, structural comparison of ESS-complex with a binary complex with NADP(+) of SpSSADH indicated that the substrate inhibition was induced by the binding of inhibitory SSA in the cofactor-binding site, instead of NADP(+). Our results provide first structure-based molecular insights into the substrate inhibition mechanism of SpSSADH as the Gram-positive bacterial SSADH. PMID:25888791
Severe Soft Tissue Infection Caused by a Non-Beta-Hemolytic Streptococcus pyogenes Strain Harboring a Premature Stop Mutation in the sagC Gene
Gerlach, Roman G.; Ensser, Armin; Dahesh, Samira; Popp, Isabel; Heeg, Christiane; Bleiziffer, Oliver; Merz, Thomas; Schulz, Theresia; Horch, Raymund E.; Bogdan, Christian; Nizet, Victor; van der Linden, Mark
We recovered a non-beta-hemolytic Streptococcus pyogenes strain from a severe soft tissue infection. In this isolate, we detected a premature stop codon within the sagC gene of the streptolysin S (SLS) biosynthetic operon. Reintroduction of full-length sagC gene on a plasmid vector restored the beta-hemolytic phenotype to our clinical isolate, indicating that the point mutation in sagC accounted for loss of hemolytic activity. To the best of our knowledge, this is the first report to demonstrate that a severe soft tissue infection can be caused by a non-beta-hemolytic S. pyogenes strain lacking a functional SagC. PMID:23515542
Immunochemical studies and complete amino acid sequence of the streptokinase from Streptococcus pyogenes (group A) M type 12 strain A374.
Ohkuni, H; Todome, Y; Suzuki, H; Mizuse, M; Kotani, N; Horiuchi, K; Shikama, N; Tsugita, A; Johnston, K H
The complete amino acid sequence of the streptokinase (SKase) of Streptococcus pyogenes M type 12 strain A374, isolated from a patient with poststreptococcal glomerulonephritis (PSGN), was determined. The epitope domain for the monoclonal antibody N-59, which cross-reacts with SKases of both the PSGN-associated strain and S. equisimilis H46A (a non-PSGN-associated strain), was predicted to be localized in residues 370 to 374. The epitope domain specific for monoclonal antibody RU-1, which reacts only with the PSGN-associated SKase, was localized to residues 164 to 236. Images PMID:1370275
Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence.
Bao, Yunjuan; Liang, Zhong; Booyjzsen, Claire; Mayfield, Jeffrey A; Li, Yang; Lee, Shaun W; Ploplis, Victoria A; Song, Hui; Castellino, Francis J
The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF(-)) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ?M23ND.1 to ?M23ND.4, harboring genes encoding streptococcal superantigen (ssa), streptococcal pyrogenic exotoxins (speC, speH, and speI), and DNases (spd1 and spd3), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The covS sensor in M23ND was identified as a pseudogene, resulting in the attenuation of speB function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (mga), M protein (emm23), C5a peptidase (scpA), fibronectin-binding proteins (sfbI and fbp54), streptolysin O (slo), hyaluronic acid capsule (hasA), streptokinase (ska), and DNases (spd and spd3), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors. PMID:25225265
Arginine deprivation by arginine deiminase of Streptococcus pyogenes controls primary glioblastoma growth in vitro and in vivo.
Fiedler, Tomas; Strauss, Madlen; Hering, Silvio; Redanz, Ulrike; William, Doreen; Rosche, Yvonne; Classen, Carl Friedrich; Kreikemeyer, Bernd; Linnebacher, Michael; Maletzki, Claudia
Arginine auxotrophy constitutes a weak point of several tumors, among them glioblastoma multiforme (GBM). Hence, those tumors are supposed to be sensitive for arginine-depleting substances, such as arginine deiminase (ADI). Here we elucidated the sensitivity of patient-individual GBM cell lines toward Streptococcus pyogenes-derived ADI. To improve therapy, ADI was combined with currently established and pre-clinical cytostatic drugs. Additionally, effectiveness of local ADI therapy was determined in xenopatients. Half of the GBM cell lines tested responded well toward ADI monotherapy. In those cell lines, viability decreased significantly (up to 50 %). Responding cell lines were subjected to combination therapy experiments to test if any additive or even synergistic effects may be achieved. Such promising results were obtained in 2/3 cases. In cell lines HROG02, HROG05 and HROG10, ADI and Palomid 529 combinations were most effective yielding more than 70 % killing after 2 rounds of treatment. Comparable boosted antitumoral effects were observed after adding chloroquine to ADI (>60% killing). Apoptosis, as well as cell cycle dysregulation were found to play a minor role. In some, but clearly not all cases, (epi-) genetic silencing of arginine synthesis pathway genes (argininosuccinate synthetase 1 and argininosuccinate lyase) explained obtained results. In vivo, ADI as well as the combination of ADI and SAHA efficiently controlled HROG05 xenograft growth, whereas adding Palomid 529 to ADI did not further increase the strong antitumoral effect of ADI. The cumulative in vitro and in vivo results proved ADI as a very promising candidate therapeutic, especially for development of adjuvant GBM combination treatments. PMID:25774632
Unique Genomic Arrangements in an Invasive Serotype M23 Strain of Streptococcus pyogenes Identify Genes That Induce Hypervirulence
Bao, Yunjuan; Liang, Zhong; Booyjzsen, Claire; Mayfield, Jeffrey A.; Li, Yang; Lee, Shaun W.; Ploplis, Victoria A.; Song, Hui
The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF?) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ?M23ND.1 to ?M23ND.4, harboring genes encoding streptococcal superantigen (ssa), streptococcal pyrogenic exotoxins (speC, speH, and speI), and DNases (spd1 and spd3), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The covS sensor in M23ND was identified as a pseudogene, resulting in the attenuation of speB function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (mga), M protein (emm23), C5a peptidase (scpA), fibronectin-binding proteins (sfbI and fbp54), streptolysin O (slo), hyaluronic acid capsule (hasA), streptokinase (ska), and DNases (spd and spd3), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors. PMID:25225265
Differences between Macrolide-Resistant and -Susceptible Streptococcus pyogenes: Importance of Clonal Properties in Addition to Antibiotic Consumption
Silva-Costa, C.; Friăes, A.; Melo-Cristino, J.
A steady decline in macrolide resistance among Streptococcus pyogenes (group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor of emm type and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within each emm type. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics, independent of the behavior of the susceptible population. PMID:22908153
Heterologous Expression of Ralp3 in Streptococcus pyogenes M2 and M6 Strains Affects the Virulence Characteristics
Siemens, Nikolai; Kreikemeyer, Bernd
Background Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS). In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i) which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii) is Ralp3 actively lost during evolution in these serotypes. Methodology/Principal Findings We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. Conclusions/Significance Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis. PMID:23424622
Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays
Background Small non-coding RNAs (sRNAs) have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogen Streptococcus pyogenes M49 (Group A Streptococcus, GAS M49), employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases. Results We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5? rapid amplification of cDNA ends-PCR (RACE-PCR) analysis. Conclusions In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of sRNAs expressed by a given organism requires the complementary use of different methods and the investigation of several environmental conditions. Despite a high conservation of sRNA genes within streptococci, the expression of sRNAs appears to be strain specific. PMID:23062031
Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for Streptococcus pyogenes Virulence
Jin, Hong; Agarwal, Shivangi; Agarwal, Shivani; Pancholi, Vijay
ABSTRACT Streptococcal surface dehydrogenase (SDH) (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) is an anchorless major multifunctional surface protein in group A Streptococcus (GAS) with the ability to bind important mammalian proteins, including plasmin(ogen). Although several biological properties of SDH are suggestive of its possible role in GAS virulence, its direct role in GAS pathogenesis has not been ascertained because it is essential for GAS survival. Thus, it has remained enigmatic as to "how and why" SDH/GAPDH is exported onto the bacterial surface. The present investigation highlights "why" SDH is exported onto the GAS surface. Differential microarray-based genome-wide transcript abundance analysis was carried out using a specific mutant, which was created by inserting a hydrophobic tail at the C-terminal end of SDH (M1-SDHHBtail) and thus preventing its exportation onto the GAS surface. This analysis revealed downregulation of the majority of genes involved in GAS virulence and genes belonging to carbohydrate and amino acid metabolism and upregulation of those related to lipid metabolism. The complete attenuation of this mutant for virulence in the mouse model and the decreased and increased virulence of the wild-type and mutant strains postcomplementation with SDHHBtail and SDH, respectively, indicated that the SDH surface export indeed regulates GAS virulence. M1-SDHHBtail also displayed unaltered growth patterns, increased intracellular ATP concentration and Hpr double phosphorylation, and significantly reduced pH tolerance, streptolysin S, and SpeB activities. These phenotypic and physiological changes observed in the mutant despite the unaltered expression levels of established transcriptional regulators further highlight the fact that SDH interfaces with many regulators and its surface exportation is essential for GAS virulence. PMID:21628503
Virulence Gene Pool Detected in Bovine Group C Streptococcus dysgalactiae subsp. dysgalactiae Isolates by Use of a Group A S. pyogenes Virulence Microarray ?
Rato, Márcia G.; Nerlich, Andreas; Bergmann, René; Bexiga, Ricardo; Nunes, Sandro F.; Vilela, Cristina L.; Santos-Sanches, Ilda; Chhatwal, Gursharan S.
A custom-designed microarray containing 220 virulence genes of Streptococcus pyogenes (group A Streptococcus [GAS]) was used to test group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causing bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections, with the latter being used for comparative purposes, for the presence of virulence genes. All bovine and all human isolates carried a fraction of the 220 genes (23% and 39%, respectively). The virulence genes encoding streptolysin S, glyceraldehyde-3-phosphate dehydrogenase, the plasminogen-binding M-like protein PAM, and the collagen-like protein SclB were detected in the majority of both bovine and human isolates (94 to 100%). Virulence factors, usually carried by human beta-hemolytic streptococcal pathogens, such as streptokinase, laminin-binding protein, and the C5a peptidase precursor, were detected in all human isolates but not in bovine isolates. Additionally, GAS bacteriophage-associated virulence genes encoding superantigens, DNase, and/or streptodornase were detected in bovine isolates (72%) but not in the human isolates. Determinants located in non-bacteriophage-related mobile elements, such as the gene encoding R28, were detected in all bovine and human isolates. Several virulence genes, including genes of bacteriophage origin, were shown to be expressed by reverse transcriptase PCR (RT-PCR). Phylogenetic analysis of superantigen gene sequences revealed a high level (>98%) of identity among genes of bovine GCS, of the horse pathogen Streptococcus equi subsp. equi, and of the human pathogen GAS. Our findings indicate that alpha-hemolytic bovine GCS, an important mastitis pathogen and considered to be a nonhuman pathogen, carries important virulence factors responsible for virulence and pathogenesis in humans. PMID:21525223
Pyogenic granulomas are small, raised, and red bumps on the skin. The bumps have a smooth surface and may ... The exact cause of pyogenic granulomas is unknown. They often appear ... arms, or face. Pyogenic granulomas are common in children.
The Interaction of Canine Plasminogen with Streptococcus pyogenes Enolase: They Bind to One Another but What Is the Nature of the Structures Involved?
Hancock, Mark A.
For years it has been clear that plasminogen from different sources and enolase from different sources interact strongly. What is less clear is the nature of the structures required for them to interact. This work examines the interaction between canine plasminogen (dPgn) and Streptococcus pyogenes enolase (Str enolase) using analytical ultracentrifugation (AUC), surface plasmon resonance (SPR), fluorescence polarization, dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and simple pull-down reactions. Overall, our data indicate that a non-native structure of the octameric Str enolase (monomers or multimers) is an important determinant of its surface-mediated interaction with host plasminogen. Interestingly, a non-native structure of plasminogen is capable of interacting with native enolase. As far as we can tell, the native structures resist forming stable mixed complexes. PMID:22174817
[Postnatal sepsis due to group A Streptococcus in a mother and her newborn].
Jänisch, Stefanie; Germerott, Tanja; Bange, Franz-Christoph; Schmidt, Anke; Debertin, Anette Solveig
Nowadays, postnatal sepsis caused by group A Streptococcus (Str. pyogenes) is a rare condition. However, the mortality due to this uncommon disease is still high, and it has been described in the literature more frequently in the last few years. The authors present the case of a female newborn who died 15 hours after spontaneous delivery in the 40th week of gestation. Autopsy revealed a lung edema and solid lung parenchyma with normal findings of the other organs on macroscopic examination. Additional bacteriological testing detected Streptococcus pyogenes in the child. Aspiration pneumonia and signs of sepsis were discovered in the histological examination. Three days postpartum, the mother was hospitalized with Streptococcus pyogenes sepsis. Streptococcus pyogenes colonization of the mother's vaginal flora was assumed to be the origin of the infection. The problem in this case was the macromorphological diagnosis of sepsis and pneumonia in the newborn. The importance of microbiological analysis as a matter of routine is emphasized. PMID:19938405
Streptococcus pyogenes c-di-AMP Phosphodiesterase, GdpP, Influences SpeB Processing and Virulence
Cho, Kyu Hong; Kang, Song Ok
Small cyclic nucleotide derivatives are employed as second messengers by both prokaryotes and eukaryotes to regulate diverse cellular processes responding to various signals. In bacteria, c-di-AMP has been discovered most recently, and some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide derivative as a second messenger instead of c-di-GMP, a well-studied important bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has not been examined yet. To test the cellular role of GdpP, we created a strain with a nonpolar inframe deletion of the gdpP gene, and examined the properties of the strain including virulence. From this study, we demonstrated that GdpP influences the biogenesis of SpeB, the major secreted cysteine protease, at a post-translational level, susceptibility to the beta lactam antibiotic ampicillin, and is necessary for full virulence in a murine subcutaneous infection model. PMID:23869242
Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor*
Pancholi, Vijay; Boël, Gregory; Jin, Hong
Cell division and cell wall synthesis are closely linked complex phenomena and play a crucial role in the maintenance and regulation of bacterial virulence. Eukaryotic-type Ser/Thr kinases reported in prokaryotes, including that in group A Streptococcus (GAS) (Streptococcus pyogenes Ser/Thr kinase (SP-STK)), regulate cell division, growth, and virulence. The mechanism of this regulation is, however, unknown. In this study, we demonstrated that SP-STK-controlled cell division is mediated under the positive regulation of secretory protein that possesses a cysteine and histidine-dependent aminohydrolases/peptidases (CHAP) domain with functionally active cell wall hydrolase activity (henceforth named as CdhA (CHAP-domain-containing and chain-forming cell wall hydrolase). Deletion of the CdhA-encoding gene resulted in severe cell division and growth defects in GAS mutants. The mutant expressing the truncated CdhA (devoid of the CHAP domain), although displayed no such defects, it became attenuated for virulence in mice and highly susceptible to cell wall-acting antibiotics, as observed for the mutant lacking CdhA. When CdhA was overexpressed in the wild-type GAS as well as in heterologous strains, Escherichia coli and Staphylococcus aureus, we observed a distinct increase in bacterial chain length. Our data reveal that CdhA is a multifunctional protein with a major function of the N-terminal region as a cell division plane-recognizing domain and that of the C-terminal CHAP domain as a virulence-regulating domain. CdhA is thus an important therapeutic target. PMID:20643653
Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes.
Kapur, V; Majesky, M W; Li, L L; Black, R A; Musser, J M
Streptococcal pyrogenic exotoxin B (SPE B), a conserved extracellular cysteine protease expressed by the human pathogenic bacterium Streptococcus pyogenes, was purified and shown to cleave inactive human interleukin 1 beta precursor (pIL-1 beta) to produce biologically active IL-1 beta. SPE B cleaves pIL-1 beta one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1 beta resulting from cleavage of pIL-1 beta by SPE B induced nitric oxide synthase activity in vascular smooth muscle cells and killed of the human melanoma A375 line. Two additional naturally occurring SPE B variants cleaved pIL-1 beta in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL-1 beta from inactive pIL-1 beta, our data add a further dimension to an emerging theme in microbial pathogenesis that bacterial and viral virulence factors act directly on host cytokine pathways. The data also contribute to an enlarging literature demonstrating that microbial extracellular cysteine proteases are important in host-parasite interactions. Images Fig. 1 Fig. 2 Fig. 4 PMID:7689226
Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop
González-Páez, Gonzalo E.; Wolan, Dennis W. (Scripps)
Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 {angstrom} resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC{sub 50} values for trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.
Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop
González-Páez, Gonzalo E.; Wolan, Dennis W.
Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 ? resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC50 values for trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products. PMID:22645124
Identification and characterization of two temperature-induced surface-associated proteins of Streptococcus suis with high homologies to members of the arginine deiminase system of Streptococcus pyogenes
Nora Winterhoff; Ralph Goethe; Petra Gruening; Manfred Rohde; Henryk Kalisz; Hilde E. Smith; Peter Valentin-Weigand
The present study was performed to identify stress-induced putative virulence proteins of Streptococcus suis. For this, protein expression patterns of streptococci grown at 32, 37, and 42°C were compared by one- and two-dimensional gel electrophoresis. Temperature shifts from 32 and 37 to 42°C induced expression of two cell wall-associated proteins with apparent molecular masses of approximately 47 and 53 kDa.
Crystal Structure of Peroxide Stress Regulator from Streptococcus pyogenes Provides Functional Insights into the Mechanism of Oxidative Stress Sensing*
Makthal, Nishanth; Rastegari, Sheila; Sanson, Misu; Ma, Zhen; Olsen, Randall J.; Helmann, John D.; Musser, James M.; Kumaraswami, Muthiah
Regulation of oxidative stress responses by the peroxide stress regulator (PerR) is critical for the in vivo fitness and virulence of group A Streptococcus. To elucidate the molecular mechanism of DNA binding, peroxide sensing, and gene regulation by PerR, we performed biochemical and structural characterization of PerR. Sequence-specific DNA binding by PerR does not require regulatory metal occupancy. However, metal binding promotes higher affinity PerR-DNA interactions. PerR metallated with iron directly senses peroxide stress and dissociates from operator sequences. The crystal structure revealed that PerR exists as a homodimer with two metal-binding sites per subunit as follows: a structural zinc site and a regulatory metal site that is occupied in the crystals by nickel. The regulatory metal-binding site in PerR involves a previously unobserved HXH motif located in its unique N-terminal extension. Mutational analysis of the regulatory site showed that the PerR metal ligands are involved in regulatory metal binding, and integrity of this site is critical for group A Streptococcus virulence. Interestingly, the metal-binding HXH motif is not present in the structurally characterized members of ferric uptake regulator (Fur) family but is fully conserved among PerR from the genus Streptococcus. Thus, it is likely that the PerR orthologs from streptococci share a common mechanism of metal binding, peroxide sensing, and gene regulation that is different from that of well characterized PerR from Bacillus subtilis. Together, our findings provide key insights into the peroxide sensing and regulation of the oxidative stress-adaptive responses by the streptococcal subfamily of PerR. PMID:23645680
Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media
Di Pierro, Francesco; Donato, Guido; Fomia, Federico; Adami, Teresa; Careddu, Domenico; Cassandro, Claudia; Albera, Roberto
Background The oral probiotic Streptococcus salivarius K12 has been shown clearly to antagonize the growth of Streptococcus pyogenes, the most important bacterial cause of pharyngeal infections in humans, by releasing two bacteriocins named salivaricin A2 and salivaricin B. Unpublished observations indicate that it can also antagonize the growth of other bacteria involved in acute otitis media. Because of its ability to colonize the oral cavity and its safety profile, we have tested its efficacy in reducing the incidence of streptococcal pharyngitis and/or tonsillitis and episodes of acute otitis media. Methods We enrolled 82 children, including 65 with and 17 without a recent diagnosis of recurrent oral streptococcal pathology. Of those with recurrent pathology, 45 were treated daily for 90 days with an oral slow-release tablet containing five billion colony-forming units of S. salivarius K12 (Bactoblis®), and the remaining 20 served as an untreated control group. The 17 children without a recent diagnosis of recurrent oral pathology were used as an additional control group. After 90 days of treatment, a 6-month follow-up period without treatment was included to evaluate a possible persistent protective role for the previously administered product. Results The 41 children who completed the 90-day course of Bactoblis showed a reduction in their episodes of streptococcal pharyngeal infection (about 90%) and/or acute otitis media (about 40%), calculated by comparing infection rates in the previous year. The 90-day treatment also reduced the reported incidence of pharyngeal and ear infections by about 65% in the 6-month follow-up period during which the product was not administered. Subjects tolerated the product well, with no side effects or dropouts reported. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal pathology reduced episodes of streptococcal pharyngeal infections and/or tonsillitis as well as episodes of acute otitis media. PMID:23233809
Superantigen-like gene(s) in human pathogenic Streptococcus dysgalactiae, subsp. equisimilis: genomic localisation of the gene encoding streptococcal pyrogenic exotoxin G ( speG dys )
Svea Sachse; Peter Seidel; Dieter Gerlach; Elisabeth Günther; Jürgen Rödel; Eberhard Straube; Karl-Hermann Schmidt
Streptococcus pyogenes (GAS) causes about 90% of streptococcal human infections while group C (GCS) and G (GGS) streptococci can be pathogenic for different mammalians. Especially the human pathogenic GCS and GGS, Streptococcus dysgalactiae, subsp. equisimilis, account for 5–8% of the human streptococcal diseases like wound infections, otitis media, purulent pharyngitis and also streptococcal toxic shock syndrome. A defined superantigen so
Mga Is Sufficient To Activate Transcription In Vitro of sof-sfbX and Other Mga-Regulated Virulence Genes in the Group A Streptococcus
Audry C. Almengor; Matthew S. Walters; Kevin S. McIver
The group A streptococcus (GAS), or Streptococcus pyogenes, is a strict human pathogen of medical signif- icance, causing infections ranging from pharyngitis (strep throat) to necrotizing fasciitis (flesh-eating disease). Several virulence genes that encode factors important for colonization, internalization, and immune evasion are under the control of the multiple gene regulator of the GAS, or Mga. Mga functions as a
Pathological fracture and pyogenic osteomyelitis in a patient with type 2 Gaucher disease.
Hayashi, Anri; Kawakita, Rie; Kumada, Tomohiro; Nozaki, Fumihito; Hiejima, Ikuko; Miyajima, Tomoko; Kusunoki, Takashi; Fujii, Tatsuya
In Gaucher disease (GD), enzyme replacement therapy (ERT) results in the alleviation of hematological abnormalities and visceral infiltration as well as improvement in quality of life and life-span. However, several years may be required for skeletal manifestations, which are usually observed in type 1 and 3 GD, to respond to ERT. Infants with type 2 GD rarely present skeletal manifestations because most of these patients die within the first 2 years of life before they develop skeletal involvement. The use of ERT may prolong the lifespan of these patients and influence the natural history of the disease. The present study reports a new natural history of treated GD in which a 2-year and 7-month-old girl with type 2 GD who was receiving ERT developed valproate-induced Fanconi syndrome, pathological fractures, and pyogenic osteomyelitis. In conclusion, skeletal disease may occur in any type of GD, and Fanconi syndrome may lead to severe skeletal complications in patients with GD. PMID:24412634
Adhesin competence repressor (AdcR) from Streptococcus pyogenes controls adaptive responses to zinc limitation and contributes to virulence
Sanson, Misu; Makthal, Nishanth; Flores, Anthony R.; Olsen, Randall J.; Musser, James M.; Kumaraswami, Muthiah
Altering zinc bioavailability to bacterial pathogens is a key component of host innate immunity. Thus, the ability to sense and adapt to the alterations in zinc concentrations is critical for bacterial survival and pathogenesis. To understand the adaptive responses of group A Streptococcus (GAS) to zinc limitation and its regulation by AdcR, we characterized gene regulation by AdcR. AdcR regulates the expression of 70 genes involved in zinc acquisition and virulence. Zinc-bound AdcR interacts with operator sequences in the negatively regulated promoters and mediates differential regulation of target genes in response to zinc deficiency. Genes involved in zinc mobilization and conservation are derepressed during mild zinc deficiency, whereas the energy-dependent zinc importers are upregulated during severe zinc deficiency. Further, we demonstrated that transcription activation by AdcR occurs by direct binding to the promoter. However, the repression and activation by AdcR is mediated by its interactions with two distinct operator sequences. Finally, mutational analysis of the metal ligands of AdcR caused impaired DNA binding and attenuated virulence, indicating that zinc sensing by AdcR is critical for GAS pathogenesis. Together, we demonstrate that AdcR regulates GAS adaptive responses to zinc limitation and identify molecular components required for GAS survival during zinc deficiency. PMID:25510500
Extracellular Cysteine Protease Produced by Streptococcus pyogenes Participates in the Pathogenesis of Invasive Skin Infection and Dissemination in Mice
Lukomski, Slawomir; Montgomery, Charles A.; Rurangirwa, Jacqueline; Geske, Robert S.; Barrish, James P.; Adams, Gerald J.; Musser, James M.
The role of an extracellular cysteine protease encoded by the speB gene in group A Streptococcus (GAS) skin infection was studied with a mouse model. Mice were injected subcutaneously with a wild-type GAS serotype M3 strain or a cysteine protease-inactivated isogenic derivative grown to stationary phase. The mortality rate of mice injected with the M3 speB mutant strain was significantly decreased (P < 0.0008) compared to that of animals injected with the wild-type parental organism. The abscesses formed in animals infected with the cysteine protease mutant strain were significantly smaller (P < 0.0001) than those caused by the wild-type organism and slowly regressed over 3 to 4 weeks. In striking contrast, infection with the wild-type GAS isolate generated necrotic lesions, and in some animals the GAS disseminated widely from the injection site and produced extensive cutaneous damage. All of these animals developed bacteremia and died. GAS dissemination was accompanied by severe tissue and blood vessel necrosis. Cysteine protease expression in the infected tissue was identified by immunogold electron microscopy. These data demonstrate that cysteine protease expression contributes to soft tissue pathology, including necrosis, and is required for efficient systemic dissemination of the organism from the initial site of skin inoculation. PMID:10085018
Streptococcus pyogenes emm Types and Clusters during a 7-Year Period (2007 to 2013) in Pharyngeal and Nonpharyngeal Pediatric Isolates.
Koutouzi, F; Tsakris, A; Chatzichristou, P; Koutouzis, E; Daikos, G L; Kirikou, E; Petropoulou, N; Syriopoulou, V; Michos, A
Group A streptococcus (GAS) is an important cause of morbidity and mortality worldwide. Surveillance of emm types has important implications, as it can provide baseline information for possible implementation of vaccination. A total of 1,349 GAS pediatric isolates were collected during a 7-year period (2007 to 2013); emm typing was completed for 1,282 pharyngeal (84%) or nonpharyngeal (16%) isolates, and emm clusters and temporal changes were analyzed. Thirty-five different emm types, including 14 subtypes, were identified. The most prevalent emm types identified were 1 (16.7%), 12 (13.6%), 77 (10.9%), 4 (10.8%), 28 (10.4%), 6 (6.8%), 3 (6.6%), and 89 (6.6%), accounting for 82.3% of total isolates. Rheumatogenic emm types comprised 16.3% of total isolates. The emm types 12, 4, and 77 were more prevalent among pharyngeal isolates, and the emm types 1, 89, 6, 75, and 11 were more prevalent among nonpharyngeal isolates. The emm types identified belonged to 13 emm clusters, and the 8 most prevalent clusters comprised 97% of all isolates. There were statistically significant decreases in the prevalence of emm types 12, 4, 5, and 61 and increases in the prevalence of emm types 89, 75, and 11, compared with the period 2001 to 2006. The proposed 30-valent GAS vaccine, which is currently in preclinical studies, encompasses 97.2% of the emm types detected in our study and 97.4% of the erythromycin-resistant strains. In addition, it includes 93.3% of the emm types involved in bacteremia. A much greater diversity of GAS emm types was identified in our area than described previously. Seasonal fluctuations and the introduction of new emm types were observed. Continuous surveillance of emm types is needed in order to evaluate the possible benefits of an M protein-based GAS vaccine. PMID:25878351
Epethelial Presence of Trueperella pyogenes Predicts Site-Level Presence of Cranial Abscess Disease in White-Tailed Deer (Odocoileus virginianus)
Belser, Emily H.; Cohen, Bradley S.; Keeler, Shamus P.; Killmaster, Charles H.; Bowers, John W.; Miller, Karl V.
Cranial/intracranial abscess disease is an emerging source of significant mortality for male white-tailed deer (Odocoileus virginianus). Most cases of cranial/intracranial abscess disease are associated with infection by the opportunistic pathogen Trueperella pyogenes although the relationship between the prevalence of the bacteria and occurrence of disease is speculative. We examined 5,612 hunter-harvested deer from 29 sites across all physiographic provinces in Georgia for evidence of cranial abscess disease and sampled the forehead, lingual, and nasal surfaces from 692 deer. We used polymerase chain reaction (PCR) to determine presence of T. pyogenes from these samples. We found T. pyogenes prevalence at a site was a predictor for the occurrence of cranial abscess disease. Prevalence of T. pyogenes did not differ between samples from the nose or tongue although prevalence along the forehead was greater for males than females (p = 0.04), particularly at sites with high occurrence of this disease. Socio-sexual behaviors, bacterial prevalence, or physiological characteristics may predispose male deer to intracranial/cranial abscess disease. Determination of factors that affect T. pyogenes prevalence among sites may help explain the occurrence of this disease among populations. PMID:25803047
Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes.
Arcus, V L; Proft, T; Sigrell, J A; Baker, H M; Fraser, J D; Baker, E N
Bacterial superantigens (SAgs) are a structurally related group of protein toxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They are implicated in a range of human pathologies associated with bacterial infection whose symptoms result from SAg-mediated stimulation of a large number (2-20%) of T-cells. At the molecular level, bacterial SAgs bind to major histocompatability class II (MHC-II) molecules and disrupt the normal interaction between MHC-II and T-cell receptors (TCRs). We have determined high-resolution crystal structures of two newly identified streptococcal superantigens, SPE-H and SMEZ-2. Both structures conform to the generic bacterial superantigen folding pattern, comprising an OB-fold N-terminal domain and a beta-grasp C-terminal domain. SPE-H and SMEZ-2 also display very similar zinc-binding sites on the outer concave surfaces of their C-terminal domains. Structural comparisons with other SAgs identify two structural sub-families. Sub-families are related by conserved core residues and demarcated by variable binding surfaces for MHC-II and TCR. SMEZ-2 is most closely related to the streptococcal SAg SPE-C, and together they constitute one structural sub-family. In contrast, SPE-H appears to be a hybrid whose N-terminal domain is most closely related to the SEB sub-family and whose C-terminal domain is most closely related to the SPE-C/SMEZ-2 sub-family. MHC-II binding for both SPE-H and SMEZ-2 is mediated by the zinc ion at their C-terminal face, whereas the generic N-terminal domain MHC-II binding site found on many SAgs appears not to be present. Structural comparisons provide evidence for variations in TCR binding between SPE-H, SMEZ-2 and other members of the SAg family; the extreme potency of SMEZ-2 (active at 10(-15) g ml-1 levels) is likely to be related to its TCR binding properties. The smez gene shows allelic variation that maps onto a considerable proportion of the protein surface. This allelic variation, coupled with the varied binding modes of SAgs to MHC-II and TCR, highlights the pressure on SAgs to avoid host immune defences. PMID:10860729
Consequences of the variability of the CovRS and RopB regulators among Streptococcus pyogenes causing human infections
Friăes, Ana; Pato, Catarina; Melo-Cristino, José; Ramirez, Mario
To evaluate the importance of covRS and ropB mutations in invasive disease caused by Group A Streptococci (GAS), we determined the sequence of the covRS and ropB genes of 191 isolates from invasive infections and pharyngitis, comprising a diverse set of emm types and multilocus sequence types. The production of SpeB and the activity of NAD glycohydrolase (NADase) and streptolysin S (SLS) were evaluated. The results support the acquisition of null covS alleles (predicted to eliminate protein function), resulting in downregulation of SpeB and upregulation of NADase and SLS, as a mechanism possibly contributing to higher invasiveness. Among the isolates tested, this mechanism was found to be uncommon (10% of invasive isolates) and was not more prevalent among clones with enhanced invasiveness (including M1T1) but occurred in diverse genetic backgrounds. In lineages such as emm64, these changes did not result in upregulation of NADase and SLS, highlighting the diversity of regulatory pathways in GAS. Despite abrogating SpeB production, null alleles in ropB were not associated with invasive infection. The covRS and ropB genes are under stabilising selection and no expansion of isolates carrying null alleles has been observed, suggesting that the presence of these regulators is important for overall fitness. PMID:26174161
The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module*
Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H. P.; Whisstock, James C.; Baker, Edward N.; Kreikemeyer, Bernd
Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 ? resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly ?-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain. PMID:22977243
Mutations in the Control of Virulence Sensor Gene from Streptococcus pyogenes after Infection in Mice Lead to Clonal Bacterial Variants with Altered Gene Regulatory Activity and Virulence
Mayfield, Jeffrey A.; Liang, Zhong; Agrahari, Garima; Lee, Shaun W.; Donahue, Deborah L.; Ploplis, Victoria A.; Castellino, Francis J.
The cluster of virulence sensor (CovS)/responder (CovR) two-component operon (CovRS) regulates ?15% of the genes of the Group A Streptococcal pyogenes (GAS) genome. Bacterial clones containing inactivating mutations in the covS gene have been isolated from patients with virulent invasive diseases. We report herein an assessment of the nature and types of covS mutations that can occur in both virulent and nonvirulent GAS strains, and assess whether a nonvirulent GAS can attain enhanced virulence through this mechanism. A group of mice were infected with a globally-disseminated clonal M1T1 GAS (isolate 5448), containing wild-type (WT) CovRS (5448/CovR+S+), or less virulent engineered GAS strains, AP53/CovR+S+ and Manfredo M5/CovR+S+. SpeB negative GAS clones from wound sites and/or from bacteria disseminated to the spleen were isolated and the covS gene was subjected to DNA sequence analysis. Numerous examples of inactivating mutations were found in CovS in all regions of the gene. The mutations found included frame-shift insertions and deletions, and in-frame small and large deletions in the gene. Many of the mutations found resulted in early translation termination of CovS. Thus, the covS gene is a genomic mutagenic target that gives GAS enhanced virulence. In cases wherein CovS? was discovered, these clonal variants exhibited high lethality, further suggesting that randomly mutated covS genes occur during the course of infection, and lead to the development of a more invasive infection. PMID:24968349
Gordon, G.; Kabins, S.A.
Seven definite and three probable cases of pyogenic sacroiliitis are presented and compared to 72 cases found in the English literature. Patients may present with a subacute localized or an acute systemic illness. Six of our patients were parenteral drug abusers. Sacroiliac uptake of gallium 67 citrate and/or technetium 99m pyrophosphate suggested the diagnosis which was confirmed by fluoroscopically controlled joint aspiration when blood cultures were sterile. Gram-negative organisms, group B streptococci and a Staphylococcus were isolated. Antibiotic treatment for four to six weeks was uniformly successful. Surgery should be reserved for abscess or sequestrum formation, neither of which were encountered in this series.
Arcanobacterium pyogenes mastitis in an 18-month-old heifer
AK Quinn; JJ Vermunt; DP Twiss
ExtractIn New Zealand, the agent Arcanobacterium (formerly Actinomyces) pyogenes is commonly associated with suppurative diseases in cattle, including abscesses, chronic endometritis and embolic pneumonia, but is an uncommon pathogen in bovine mastitis. Overseas, A. pyogenes mastitis is widespread and usually sporadic. The source of infection is considered to be endogenous, as A. pyogenes can be recovered from the mucous membranes,
Cloning and expression in Escherichia coli of the streptolysin O determinant from Streptococcus pyogenes: characterization of the cloned streptolysin O determinant and demonstration of the absence of substantial homology with determinants of other thiol-activated toxins.
Kehoe, M; Timmis, K N
A gene bank of Streptococcus pyogenes Richards was constructed in Escherichia coli by using the bacteriophage replacement vector lambda L47.1, and hybrid phage expressing streptolysin O (SLO) were identified among the recombinants. DNA sequences encoding SLO were subcloned from an slo+ hybrid phage into a low-copy-number vector plasmid to yield an slo+ hybrid plasmid, pMK157. This plasmid contains 5.6 kilobase pairs of cloned streptococcal DNA sequences, is stable, and expresses SLO at easily detectable levels in E. coli. Transposon gamma delta insertion mutants and in vitro-generated deletion mutants of pMK157 were isolated and analyzed. This analysis showed that a single gene is sufficient for production of SLO in E. coli and allowed this slo gene to be mapped to within +/- 100 base pairs. Two forms of the slo gene product, with molecular weights of 68,000 and 61,000, were detected in E. coli minicells harboring slo+ plasmids and by immunoblotting of E. coli whole cells harboring slo+ plasmids. Southern blotting hybridization experiments with the cloned SLO DNA sequences as probes failed to demonstrate homology between the cloned SLO determinant and DNA isolated from bacteria expressing thiol-activated cytolysins related to SLO. Images PMID:6321351
Crystal structure of peptidyl-tRNA hydrolase from a Gram-positive bacterium, Streptococcus pyogenes at 2.19 Ĺ resolution shows the closed structure of the substrate-binding cleft
Singh, Avinash; Gautam, Lovely; Sinha, Mau; Bhushan, Asha; Kaur, Punit; Sharma, Sujata; Singh, T.P.
Peptidyl-tRNA hydrolase (Pth) catalyses the release of tRNA and peptide components from peptidyl-tRNA molecules. Pth from a Gram-positive bacterium Streptococcus pyogenes (SpPth) was cloned, expressed, purified and crystallised. Three-dimensional structure of SpPth was determined by X-ray crystallography at 2.19 Ĺ resolution. Structure determination showed that the asymmetric unit of the unit cell contained two crystallographically independent molecules, designated A and B. The superimposition of C? traces of molecules A and B showed an r.m.s. shift of 0.4 Ĺ, indicating that the structures of two crystallographically independent molecules were identical. The polypeptide chain of SpPth adopted an overall ?/? conformation. The substrate-binding cleft in SpPth is formed with three loops: the gate loop, Ile91–Leu102; the base loop, Gly108–Gly115; and the lid loop, Gly136–Gly150. Unlike in the structures of Pth from Gram-negative bacteria, the entry to the cleft in the structure of SpPth appeared to be virtually closed. However, the conformations of the active site residues were found to be similar. PMID:25389518
The toxins of group A streptococcus, the flesh eating bacteria.
Stevens, D L
Streptococcus pyogenes causes a wide variety of infections in individuals of all ages in most countries of the world. Because of the frequency with which these infections occur, physicians are quite familiar with the diversity of clinical presentations associated with the Group A streptococcus. Yet in the late 1980's, a severe form of streptococcal infection, the Streptococcal Toxic Shock Syndrome, emerged and has persisted for the last 10 years. This syndrome is associated with invasive soft tissue infections and the early onset of shock and organ failure. The purpose of this paper is to briefly describe the epidemiologic and clinical features of the Streptococcal Toxic Shock Syndromes and to emphasize the role that toxins produced by S. pyogenes play in the pathogenesis of this disease. PMID:9037618
Streptococcus acidominimus causing invasive disease in humans: a case series
Introduction Streptococcus acidominimus is a member of the viridans group streptococci and is rarely pathogenic in humans, making it difficult to assess its epidemiologic and clinical significance. Case presentation We report the cases of five Han Chinese patients with invasive diseases caused by S. acidominimus over a one-year time frame. Three of the patients developed continuous fever after surgery, consisting of a successful elective laparoscopic cholecystectomy (case 1), a laparoscopic esophageal resection and gastroesophageal anastomosis (case 2), and a liver transplant in a patient with liver cancer (case 3). For these three patients, cultures of the purulent drainage material grew S. acidominimus. Case 4 concerns a 52-year-old man who developed sepsis 48 hours after hospitalization for hepatitis, liver cirrhosis and hepatitis-related glomerulonephritis. Case 5 concerns a 55-year-old woman receiving regular hemodialysis who had low-grade fever for one month. For these two patients, blood cultures grew S. acidominimus. An antimicrobial susceptibility test revealed that S. acidominimus was resistant to clindamycin and, to some degree, beta-lactam or macrolides. The S. acidominimus from the patient on hemodialysis was resistant to multiple antibiotics. Conclusion S. acidominimus is an ever-increasing cause of disease, especially in patients who are critically ill. It is showing increased resistance to antimicrobial agents, so in patients with viridans group streptococci infections, it is necessary to identify the species to improve the clinical management of S. acidominimus. PMID:24529345
Complete genome sequence of a virulent Streptococcus agalactiae strain 138P isolated from diseased Nile tilapia
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus agalactiae strain 138P was isolated from the kidney of diseased Nile tilapia in Idaho during a 2007 streptococcal disease outbreak. The full genome of S. agalactiae 138P is 1,838,716 bp. The availability of this genome will allow comparative genomics to identify genes for antigen disco...
Complete Genome Sequence of a Virulent Streptococcus agalactiae Strain, 138P, Isolated from Diseased Nile Tilapia.
Pridgeon, Julia W; Zhang, Dunhua
Streptococcus agalactiae strain 138P was isolated from the kidney of diseased Nile tilapia in Idaho during a 2007 streptococcal disease outbreak. The full genome sequence of S. agalactiae 138P is 1,838,701 bp. The availability of this genome will allow comparative genomics analysis to identify genes for antigen discovery and vaccine development. PMID:24744333
Complete Genome Sequence of a Virulent Strain, Streptococcus iniae ISET0901, Isolated from Diseased Tilapia.
Pridgeon, Julia W; Zhang, Dunhua; Zhang, Lee
Streptococcus iniae ISET0901 is a virulent strain isolated in 2007 from diseased tilapia. Its full genome is 2,070,856 bp. The availability of this genome will allow comparative genomics to identify virulence genes important for the pathogenesis of streptococcosis caused by S. iniae, as well as possible immunogens for vaccine development. PMID:24903878
Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease
Russell W. Steele; Rajasekharan Warrier; Patrick J. Unkel; Bertrand J. Foch; Richard F. Howes; Sanjay Shah; Karen Williams; Sheila Moore; Sue J. Jue
OBJECTIVE: Because of a susceptibility to severe pneumococcal infection, children with sickle cell disease (SCD) routinely receive penicillin prophylaxis. Increasing rates of penicillin resistance have been reported throughout the world. Our objective was to assess the prevalence of nasopharyngeal colonization with Streptococcus pneumoniae and to assess the antimicrobial susceptibility of the organisms in children with SCD. STUDY DESIGN: Nasopharyngeal cultures
Group A Streptococcus Endometritis following Medical Abortion
Gendron, Nicolas; Joubrel, Caroline; Nedellec, Sophie; Campagna, Jennifer; Agostini, Aubert; Doucet-Populaire, Florence; Casetta, Anne; Raymond, Josette; Kernéis, Solen
Medical abortion is not recognized as a high-risk factor for invasive pelvic infection. Here, we report two cases of group A Streptococcus (GAS; Streptococcus pyogenes) endometritis following medical abortions with a protocol of oral mifepristone and misoprostol. PMID:24829245
The Arcanobacterium pyogenes Collagen-Binding Protein, CbpA, Promotes Adhesion to Host Cells
Paula A. Esmay; Stephen J. Billington; Malen A. Link; J. Glenn Songer; B. Helen Jost
Arcanobacterium pyogenes is an opportunistic pathogen associated with suppurative diseases in economically important food animals such as cattle, pigs, and turkeys. A. pyogenes adheres to host epithelial cells, and adhesion is promoted by the action of neuraminidase, which is expressed by this organism. However, a neuraminidase-deficient mutant of A. pyogenes only had a reduced ability to adhere to host epithelial
Arcanobacterium pyogenes : molecular pathogenesis of an animal opportunist
B. Helen Jost; Stephen J. Billington
Arcanobacterium pyogenes is a commensal and an opportunistic pathogen of economically important livestock, causing diseases as diverse as mastitis, liver abscessation and pneumonia. This organism possesses a number of virulence factors that contribute to its pathogenic potential. A. pyogenes expresses a cholesterol-dependent cytolysin, pyolysin, which is a haemolysin and is cytolytic for immune cells, including macrophages. Expression of pyolysin is
Genetic relationships deduced from emm and multilocus sequence typing of invasive Streptococcus dysgalactiae subsp. equisimilis and S. canis recovered from isolates collected in the United States.
Ahmad, Yusra; Gertz, Robert E; Li, Zhongya; Sakota, Varja; Broyles, Laura N; Van Beneden, Chris; Facklam, Richard; Shewmaker, P Lynn; Reingold, Arthur; Farley, Monica M; Beall, Bernard W
Beta-hemolytic group C and G streptococci cause a considerable invasive disease burden and sometimes cause disease outbreaks. Little is known about the critical epidemiologic parameter of genetic relatedness between isolates. We determined the emm types of 334 Streptococcus dysgalactiae subsp. equisimilis isolates, and attempted emm typing of 5 Streptococcus canis isolates from a recent population-based surveillance for invasive isolates. Thirty-four emm types were observed, including one from S. canis. We formulated multilocus sequence typing (MLST) primers with six of the seven loci corresponding to the Streptococcus pyogenes MLST scheme. We performed MLST with 65 of the 334 surveillance isolates (61 S. dysgalactiae subsp. equisimilis isolates, 4 S. canis isolates) to represent each emm type identified, including 2 to 3 isolates for each of the 25 redundantly represented emm types. Forty-one MLST sequence types (STs) were observed. Isolates within 16 redundantly represented S. dysgalactiae subsp. equisimilis emm types shared identical or nearly identical STs, demonstrating concordance between the emm type and genetic relatedness. However, seven STs were each represented by two to four different emm types, and 7 of the 10 S. dysgalactiae subsp. equisimilis eBURST groups represented up to six different emm types. Thus, S. dysgalactiae subsp. equisimilis isolates were similar to S. pyogenes isolates, in that strains of the same emm type were often highly related, but they differed from S. pyogenes, in that S. dysgalactiae subsp. equisimilis strains with identical or closely similar STs often exhibited multiple unrelated emm types. The phylogenetic relationships between S. dysgalactiae subsp. equisimilis and S. pyogenes alleles revealed a history of interspecies recombination, with either species often serving as genetic donors. The four S. canis isolates shared highly homologous alleles but were unrelated clones without evidence of past recombination with S. dysgalactiae subsp. equisimilis or S. pyogenes. PMID:19386831
Pathology of Pyogenic Liver Abscess in Children
Fausto E. L. Pereira; Carlos Musso; Jane S. Castelo
Little is known about preexisting lesions in livers of children with pyogenic liver abscess (PLA). Study of these lesions\\u000a may elucidate possible predisposing factors for the disease. In Vitória, state of Espirito Santo, Brazil, PLA in children\\u000a is frequently associated with helminthic infections and eosinophilia. We hypothesize that nematode infection with larvae migrating\\u000a through the liver is a predisposing factor
Penicillin and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease
P. Joan Chesney; Judith A. Wilimas; Gerald Presbury; Seema Abbasi; Robert J. Leggiadro; Yvonne Davis; Sara W. Day; Gordon E. Schutze; Winfred C. Wang
Objective: We investigated the possibility that antimicrobial-resistant pneumococci were causing invasive disease in children with sickle-cell disease (SCD). Study design: Records of all children with SCD observed at the Mid-South Sickle Cell Center (MSSCC) at LeBonheur Children's Medical Center were reviewed from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were identified. The Streptococcus pneumoniae isolates from
Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease.
Landwehr-Kenzel, Sybille; Henneke, Philipp
Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood-brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and ?-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just emerging. PMID:25400631
Draft Genome Sequence of Streptococcus parauberis Strain SK-417, Isolated from Diseased Sebastes ventricosus in Kagoshima, Japan.
Oguro, Kazuki; Yamane, Jin; Yamamoto, Takeshi; Ohnishi, Kouhei; Oshima, Syun-Ichirou; Imajoh, Masayuki
Streptococcus parauberis strain SK-417 was isolated from the brain of a diseased Sebastes ventricosus, collected from an aquaculture farm in April 2013 in Kagoshima Prefecture, Japan. The draft genome sequence, obtained with a 454 GS Junior sequencing system, consists of 33 large contigs of >500 bp, totaling 1,958,836 bp, and has a G+C content of 35.4%. PMID:24855302
Draft Genome Sequence of Streptococcus parauberis Strain SK-417, Isolated from Diseased Sebastes ventricosus in Kagoshima, Japan
Oguro, Kazuki; Yamane, Jin; Yamamoto, Takeshi; Ohnishi, Kouhei; Oshima, Syun-ichirou
Streptococcus parauberis strain SK-417 was isolated from the brain of a diseased Sebastes ventricosus, collected from an aquaculture farm in April 2013 in Kagoshima Prefecture, Japan. The draft genome sequence, obtained with a 454 GS Junior sequencing system, consists of 33 large contigs of >500 bp, totaling 1,958,836 bp, and has a G+C content of 35.4%. PMID:24855302
Evidence of lateral gene transfer among strains of Streptococcus zooepidemicus in weanling horses with respiratory disease.
Velineni, Sridhar; Breathnach, Cormac C; Timoney, John F
Streptococcus zooepidemicus (Sz) is a tonsillar commensal of healthy horses but with potential to opportunistically invade the lower respiratory tract. Sz is genetically variable and recombinogenic based on analysis of gene sequences including szp, szm and MLST data. Although a variety of serovars of the protective SzP are commonly harbored in the tonsils of the same horse, lower respiratory infections usually involve a single clone. Nevertheless, isolation of specific clones from epizootics of respiratory disease has been recently reported in horses and dogs in N. America, Europe and Asia. In this report, we provide evidence suggestive of lateral gene exchange and recombination between strains of Sz from cases of respiratory disease secondary to experimental equine herpes 1 virus infection in an isolated group of weanling horses and ponies. Nasal swabs of 13 of 18 weanlings with respiratory disease yielded mucoid colonies of Sz following culture. Comparison of arcC, nrdE, proS, spi, tdk, tpi and yqiL of these Sz revealed 3 Clades. Clade-1 (ST-212) and 2 (ST-24) were composed of 7 and 3 isolates, respectively. ST-24 and 212 differed in all 7 housekeeping as well as szp and szm alleles. Two isolates of Clade-1 were assigned to ST-308, a single locus variant of ST-212 that contained the proS-16 allele sequenced in ST-24. One isolate of ST-308 contained szm-2, the same allele sequenced in Clade 2 isolates; the other was positive for the szp-N2HV2 allele of Clade 2. These observations are consistent with gene transfer between Sz in the natural host and may explain formation of novel clones that invade the lower respiratory tract or cause epizootics of respiratory disease in dogs and horses. PMID:24263112
Neonatal Streptococcus pneumoniae Infection May Aggravate Adulthood Allergic Airways Disease in Association with IL-17A
Yang, Ting; Jiang, Xiaoli; Zhang, Liqun; Wang, Lijia; Wang, Qinghong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou
Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-?, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production. PMID:25816135
Characterization of Streptococcus suis isolates recovered between 2008 and 2011 from diseased pigs in Québec, Canada.
Gottschalk, Marcelo; Lacouture, Sonia; Bonifait, Laetitia; Roy, David; Fittipaldi, Nahuel; Grenier, Daniel
In the present study we report the distribution of different serotypes of Streptococcus suis among strains isolated from diseased pigs in Québec, Canada, recovered between 2008 and 2011. Serotype 2 strains were further studied for the presence of the following virulence markers: suilysin (sly), muramidase-released protein (MRP), extracellular protein factor (epf) and the pilus encoded by the srtF cluster. Of 1004 field strains collected, 986 were confirmed to be S. suis by either the species-specific PCR targeting the gdh gene or by 16S rRNA gene sequencing analysis. Results showed that, although widely used, the species-specific PCR test can sometimes be misleading and fail to correctly identify some S. suis isolates. Serotypes 2, 3, 1/2, 4, 8 and 22 together represented 51% of S. suis strains (64.5% of typable strains). Results confirmed the relatively low prevalence of serotype 2 in North America, when compared to European and Asian countries. The vast majority of serotype 2 field strains (96%) belong to either the MRP(+), srtF pilus(+), epf(-), sly(-) (52%) or the MRP(-), srtF pilus(-), epf(-), sly(-) phenotypes (44%). Most non-typable strains (89%) presented high surface hydrophobicity, suggesting that these are poorly or non-encapsulated. Electron microscopy studies confirmed the lack of capsular polysaccharide in selected non-typable high hydrophobic strains. The role and pathogenesis of the infection caused by these strains remain to be elucidated. PMID:23177911
Genome Anatomy of Streptococcus parasanguinis Strain C1A, Isolated from a Patient with Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Reveals Unusual Genomic Features
Ng, Kim Tien; Pang, Yong Kek; Chong, Teik Min; Kamarulzaman, Adeeba; Yin, Wai-Fong; Tee, Kok Keng
Streptococcus parasanguinis causes invasive diseases. However, the mechanism by which it causes disease remains unclear. Here, we describe the complete genome sequence of S. parasanguinis C1A, isolated from a patient diagnosed with an acute exacerbation of chronic obstructive pulmonary disease. Several genes that might be associated with pathogenesis are also described. PMID:26021924
Streptococcus pneumoniae in Biofilms Are Unable to Cause Invasive Disease Due to Altered Virulence Determinant Production
Sanchez, Carlos J.; Kumar, Nikhil; Lizcano, Anel; Shivshankar, Pooja; Dunning Hotopp, Julie C.; Jorgensen, James H.; Tettelin, Hervé; Orihuela, Carlos J.
It is unclear whether Streptococcus pneumoniae in biofilms are virulent and contribute to development of invasive pneumococcal disease (IPD). Using electron microscopy we confirmed the development of mature pneumococcal biofilms in a continuous-flow-through line model and determined that biofilm formation occurred in discrete stages with mature biofilms composed primarily of dead pneumococci. Challenge of mice with equal colony forming units of biofilm and planktonic pneumococci determined that biofilm bacteria were highly attenuated for invasive disease but not nasopharyngeal colonization. Biofilm pneumococci of numerous serotypes were hyper-adhesive and bound to A549 type II pneumocytes and Detroit 562 pharyngeal epithelial cells at levels 2 to 11-fold greater than planktonic counterparts. Using genomic microarrays we examined the pneumococcal transcriptome and determined that during biofilm formation S. pneumoniae down-regulated genes involved in protein synthesis, energy production, metabolism, capsular polysaccharide (CPS) production, and virulence. We confirmed these changes by measuring CPS by ELISA and immunoblotting for the toxin pneumolysin and the bacterial adhesins phosphorylcholine (ChoP), choline-binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP). We conclude that biofilm pneumococci were avirulent due to reduced CPS and pneumolysin production along with increased ChoP, which is known to bind C-reactive protein and is opsonizing. Likewise, biofilm pneumococci were hyper-adhesive due to selection for the transparent phase variant, reduced CPS, and enhanced production of PsrP, CbpA, and ChoP. These studies suggest that biofilms do not directly contribute to development of IPD and may instead confer a quiescent mode of growth during colonization. PMID:22174882
Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.
Thorburn, Alison N; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M
Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells. PMID:22461699
Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants
Dangor, Ziyaad; Lala, Sanjay G.; Cutland, Clare L.; Koen, Anthonet; Jose, Lisa; Nakwa, Firdose; Ramdin, Tanusha; Fredericks, Joy; Wadula, Jeannette; Madhi, Shabir A.
Introduction Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0–6 days of life, EOD) and late-onset (7–89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. Methods A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. Results We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24–9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94–386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44–49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17–10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44–120.95) greater in cases (13.2%) than controls (0.4%). Discussion The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting. PMID:25849416
Antimicrobial Effect of Lactobacillus reuteri on Cariogenic Bacteria Streptococcus gordonii, Streptococcus mutans, and Periodontal Diseases Actinomyces naeslundii and Tannerella forsythia.
Baca-Castańón, Magda Lorena; De la Garza-Ramos, Myriam Angélica; Alcázar-Pizańa, Andrea Guadalupe; Grondin, Yohann; Coronado-Mendoza, Anahí; Sánchez-Najera, Rosa Isela; Cárdenas-Estrada, Eloy; Medina-De la Garza, Carlos Eduardo; Escamilla-García, Erandi
Lactic acid bacteria (LAB) are well known for their beneficial effects on human health in the intestine and immune system; however, there are few studies on the impact they can generate in oral health. The aim of this study was to test and compare in vitro antimicrobial activity of L. reuteri on pathogenic bacteria involved in the formation of dental caries: S. mutans, S. gordonii, and periodontal disease: A. naeslundii and T. forsythia. Also, we determined the growth kinetics of each bacterium involved in this study. Before determining the antimicrobial action of L. reuteri on cariogenic bacteria and periodontal disease, the behavior and cell development time of each pathogenic bacterium were studied. Once the conditions for good cell growth of each of selected pathogens were established according to their metabolic requirements, maximum exponential growth was determined, this being the reference point for analyzing the development or inhibition by LAB using the Kirby Bauer method. Chlorhexidine 0.12 % was positive control. L. reuteri was shown to have an inhibitory effect against S. mutans, followed by T. forsythia and S. gordonii, and a less significant effect against A. naeslundii. Regarding the effect shown by L. reuteri on the two major pathogens, we consider its potential use as a possible functional food in the prevention or treatment of oral diseases. PMID:25422124
Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae
Hervé Tettelin; Vega Masignani; Michael J. Cieslewicz; Jonathan A. Eisen; Scott Peterson; Michael R. Wessels; Ian T. Paulsen; Karen E. Nelson; Immaculada Margarit; Timothy D. Read; Lawrence C. Madoff; Alex M. Wolf; Maureen J. Beanan; Lauren M. Brinkac; Sean C. Daugherty; Robert T. Deboy; A. Scott Durkin; James F. Kolonay; Ramana Madupu; Matthew R. Lewis; Diana Radune; Nadezhda B. Fedorova; David Scanlan; Hoda Khouri; Stephanie Mulligan; Heather A. Carty; Robin T. Cline; Susan E. van Aken; John Gill; Maria Scarselli; Marirosa Mora; Emilia T. Iacobini; Cecilia Brettoni; Giuliano Galli; Massimo Mariani; Filippo Vegni; Domenico Maione; Daniela Rinaudo; Rino Rappuoli; John L. Telford; Dennis L. Kasper; Guido Grandi; Claire M. Fraser
The 2,160,267 bp genome sequence of Streptococcus agalactiae, the leading cause of bacterial sepsis, pneumonia, and meningitis in neonates in the U.S. and Europe, is predicted to encode 2,175 genes. Genome comparisons among S. agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and the other completely sequenced genomes identified genes specific to the streptococci and to S. agalactiae. These in silico analyses, combined
Complete genome sequence of a virulent Streptococcus agalactiae strain 138P isolated from disease Nile tilapia
Technology Transfer Automated Retrieval System (TEKTRAN)
The complete genome of a virulent Streptococcus agalactiae strain 138P is 1838701 bp in size, containing 1831 genes. The genome has 1593 coding sequences, 152 pseudo genes, 16 rRNAs, 69 tRNAs, and 1 non-coding RNA. The annotation of the genome is added by the NCBI Prokaryotic Genome Annotation Pipel...
Implications of Streptococcus pneumoniae Penicillin Resistance and Serotype Distribution in Kuwait for Disease Treatment and Prevention
E. M. Mokaddas; V. O. Rotimi; M. J. Albert
Received 7 July 2007\\/Returned for modification 11 September 2007\\/Accepted 20 November 2007 Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that
Mechanisms of group A Streptococcus resistance to reactive oxygen species
Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N.
Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•?), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736
Mechanisms of group A Streptococcus resistance to reactive oxygen species.
Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N
Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736
European Foul Brood: a Disease of the Larval Honeybee (Apis mellifera L.) caused by a Combination of Streptococcus pluton (Bacillus pluton White) and Bacterium eurydice White
L. Bailey
RESULTS of preliminary experiments1 have shown that European foul brood disease of the larval honeybee can be caused in bee colonies by spraying their brood with suspensions of Streptococcus pluton (Bacillus pluton White) and Bacterium eurydice White if the two organisms are grown together in mixed anaerobic culture ; fifth subcultures of a mixed culture were usually virulent, although virulence
Quantitative susceptibility of Streptococcus suis strains isolated from diseased pigs in seven European countries to antimicrobial agents licenced in veterinary medicine
Henk J. Wisselink; Kees T. Veldman; Chris Van den Eede; Sarah A. Salmon; Dik J. Mevius
The susceptibility of Streptococcus suis strains (n=384) isolated from diseased pigs in seven European countries to 10 antimicrobial agents was determined. For that purpose a microbroth dilution method was used according to CLSI recommendations. The following antimicrobial agents were tested: ceftiofur, cefquinome, enrofloxacin, florfenicol, gentamicin, penicillin, spectinomycin, tetracycline, tilmicosin and trimethoprim\\/sulphamethoxazole. Using breakpoints established by CLSI for veterinary pathogens, all
From meadows to milk to mucosa - adaptation of Streptococcus and Lactococcus species to their nutritional environments.
Price, Claire E; Zeyniyev, Araz; Kuipers, Oscar P; Kok, Jan
Lactic acid bacteria (LAB) are indigenous to food-related habitats as well as associated with the mucosal surfaces of animals. The LAB family Streptococcaceae consists of the genera Lactococcus and Streptococcus. Members of the family include the industrially important species Lactococcus lactis, which has a long history safe use in the fermentative food industry, and the disease-causing streptococci Streptococcus pneumoniae and Streptococcus pyogenes. The central metabolic pathways of the Streptococcaceae family have been extensively studied because of their relevance in the industrial use of some species, as well as their influence on virulence of others. Recent developments in high-throughput proteomic and DNA-microarray techniques, in in vivo NMR studies, and importantly in whole-genome sequencing have resulted in new insights into the metabolism of the Streptococcaceae family. The development of cost-effective high-throughput sequencing has resulted in the publication of numerous whole-genome sequences of lactococcal and streptococcal species. Comparative genomic analysis of these closely related but environmentally diverse species provides insight into the evolution of this family of LAB and shows that the relatively small genomes of members of the Streptococcaceae family have been largely shaped by the nutritionally rich environments they inhabit. PMID:22212109
Streptococcus pyogenes Sternoclavicular Septic Arthritis in a Healthy Adult
Savcic-Kos, Radmila M.; Mali, Padmavati; Abraham, Ajit; Issa, Meltiady; Rangu, Venu; Nasser, Rana
Sternoclavicular septic arthritis is a rare infection, accounting for approximately 1% of septic arthritis in the general population. Staphylococcus aureus is the predominant etiologic agent, and it usually occurs in relatively young adults with some type of predisposition to infection. We report, to the best of our knowledge, the first case of group A streptococcal, sternoclavicular arthritis in a previously healthy 62-year-old male patient. We present a detailed history and physical examination, with laboratory findings, imaging studies, cultures, and therapy. PMID:24667224
Streptococcus pyogenes activates human plasmacytoid and myeloid dendritic cells
Ville Veckman; Ilkka Julkunen
Human peripheral blood contains two major dendritic cell (DC) populations, namely CD11c-CD123 plasmacytoid DCs (PDCs) and CD11cCD123- myeloid DCs (MDCs). Although the activation of these DC types by various TLR ligands has been relatively well-characterized, less is known about the ability of whole live bacteria to induce PDC and MDC activation. In the present report, we have compared the activation
Immunological competence of children with pyogenic meningitis
Lorraine J. Beard; Y. H. Thong
A broad range of immunological tests was performed on 9 consecutive children with pyogenic meningitis. Two were found to have combined IgG and IgA deficiency. One had a combination of IgG deficiency and impaired neutrophil chemotaxis. Primary immunodeficiency disorders as a predisposing cause of pyogenic meningitis may be more common than previously suspected.
Spontaneous pyogenic vertebral osteomyelitis in nondrug users
Joan M Nolla; Javier Ariza; Carmen Gómez-Vaquero; Jordi Fiter; Joaquín Bermejo; Josep Valverde; Daniel Roig Escofet; Francesc Gudiol
Objective: To analyze the clinical, microbiological, and radiologic features of patients without drug addiction suffering from spontaneous pyogenic vertebral osteomyelitis. Methods: We collected all microbiologically proved cases of pyogenic vertebral osteomyelitis seen between January 1980 and December 1999 in a teaching hospital. Patients with prior spinal instrumentation or surgery and injection drug users were excluded. Results: Sixty-four patients, with a
Kuttel, Michelle
Bangalore, India #12;STREPTOCOCCUS PNEUMONIAE · leading cause of disease esp. in developing world for children vaccines · better immune responses in young children than polysaccharide-only vaccines · Pneumococcal Vaccine Project · development of affordable
Pyogenic Sacroiliitis and Pyomyositis in a Patient with Systemic Lupus Erythematous
Chebbi, Wafa; Jerbi, Saida; Kessomtini, Wassia; Fradi, Asma; Sfar, Mohamed Habib
Pyogenic sacroiliitis and pyomyositis are uncommon infectious diseases and their diagnoses are often delayed. They are typically seen in children and young adults and are rare in middle-aged people especially in those affected by rheumatic diseases. We present the first case of a Staphylococcus aureus related pyogenic sacroiliitis associated with iliacus and gluteal pyomyositis occurring in a patient with systemic lupus erythematosus. Antibiotic treatment was administered for a total of 6 weeks with a total recovery. Pyogenic sacroiliitis and pyomyositis, although remaining rare events, should be remembered as severe complications in immunosuppressed patients with inflammatory diseases. Early clinical suspicion, imaging diagnosis, and adequate therapy are decisive for the satisfactory outcome. PMID:25165609
A Novel Gene Involved in the Survival of Streptococcus mutans under Stress Conditions
Li, Dan; Shibata, Yukie; Takeshita, Toru
A Streptococcus mutans mutant defective in aciduricity was constructed by random-insertion mutagenesis. Sequence analysis of the mutant revealed a mutation in gidA, which is known to be involved in tRNA modification in Streptococcus pyogenes. Complementation of gidA by S. pyogenes gidA recovered the acid tolerance of S. mutans. Although the gidA-inactivated S. pyogenes mutant exhibited significantly reduced expression of multiple extracellular virulence proteins, the S. mutans mutant did not. On the other hand, the gidA mutant of S. mutans showed reduced ability to withstand exposure to other stress conditions (high osmotic pressure, high temperature, and bacitracin stress) besides an acidic environment. In addition, loss of GidA decreased the capacity for glucose-dependent biofilm formation by over 50%. This study revealed that gidA plays critical roles in the survival of S. mutans under stress conditions, including lower pH. PMID:24123744
Rapid Identification of Group A Streptococcus as the Cause of Necrotizing Fasciitis
Mark J Ault; Joel Geiderman; Richard Sokolov
Group A ?-hemolytic Streptococcus pyogenes (GAS) causes a spectrum of highly aggressive, invasive infections. We report two cases of necrotizing fasciitis in which GAS was identified as the presumptive causative organism with the use of the standard rapid streptococcal diagnostic kit. We believe the rapid test kits may be a useful adjunct in the diagnosis and treatment of this catastrophic
Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection
Marks, Laura R.; Kong, Yong; Gent, Janneane F.; Roche-Hakansson, Hazeline
Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis. PMID:25135685
Early biofilm formation on microtiter plates is not correlated with the invasive disease potential of Streptococcus pneumoniae
Lizcano, Anel; Chin, Tiffany; Sauer, Karin; Tuomanen, Elaine I.; Orihuela, Carlos J.
Biofilm formation has been suggested to play an important role during Streptococcus pneumoniae nasopharyngeal colonization and may facilitate progression to pneumonia. To test whether the ability of S. pneumoniae to form biofilms was important for virulence we screened the ability of 30 invasive and 22 non-invasive clinical isolates of serotype 6A and 6B to form early biofilms on polystyrene microtiter plates and infect mice following intranasal and intratracheal challenge. We first determined that no correlation existed between the ability to form early biofilms and whether isolates were collected from healthy carriers or individuals with invasive disease. A disconnect between biofilm forming ability and the capacity to colonize the nasopharynx, cause pneumonia, and enter the bloodstream was also observed in mice. Importantly, S. pneumoniae mutants deficient in the established virulence determinants pneumolysin, CbpA, and hydrogen peroxide formed biofilms normally. Incidentally, we determined that robust biofilm production was dependent on the formation and coalescing of bacteria aggregates on a thin layer of bacteria attached to the plate surface. In summary, these studies suggest that the ability to form early biofilms in vitro does not reflect virulence potential. More complex studies are required to determine if biofilm formation is important for virulence. PMID:20096771
Profiling of the bacteria responsible for pyogenic liver abscess by 16S rRNA gene pyrosequencing.
Song, Yun Gyu; Shim, Sang Gun; Kim, Kwang Min; Lee, Dong-Hae; Kim, Dae-Soo; Choi, Sang-Haeng; Song, Jae-Young; Kang, Hyung-Lyun; Baik, Seung-Chul; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho
Pyogenic liver abscess (PLA) is a severe disease with considerable mortality and is often polymicrobial. Understanding the pathogens that cause PLA is the basis for PLA treatment. Here, we profiled the bacterial composition in PLA fluid by pyrosequencing the 16S ribosomal RNA (rRNA) gene based on next-generation sequencing (NGS) technology to identify etiological agents of PLA and to provide information of their 16S rRNA sequences for application to DNA-based techniques in the hospital. Twenty patients with PLA who underwent percutaneous catheter drainage, abscess culture, and blood culture for isolates were included. Genomic DNAs from abscess fluids were subjected to polymerase chain reaction and pyrosequencing of the 16S rRNA gene with a 454 GS Junior System. The abscess and blood cultures were positive in nine (45%) and four (20%) patients, respectively. Pyrosequencing of 16S rRNA gene showed that 90% of the PLA fluid samples contained single or multiple genera of known bacteria such as Klebsiella, Fusobacterium, Streptococcus, Bacteroides, Prevotella, Peptostreptococcus, unassigned Enterobacteriaceae, and Dialister. Klebsiella was predominantly found in the PLA fluid samples. All samples that carried unassigned bacteria had 26.8% reads on average. We demonstrated that the occurrence of PLA was associated with eight known bacterial genera as well as unassigned bacteria and that 16S rRNA gene sequencing was more useful than conventional culture methods for accurate identification of bacterial pathogens from PLA. PMID:24871976
VACCINES TO PREVENT Streptococcus iniae AND S. agalactiae DISEASE IN NILE TILAPIA Oreochromis niloticus
Technology Transfer Automated Retrieval System (TEKTRAN)
Minimizing the effects of disease is crucial to prevent mortality, morbidity, and to promote optimal growth and feed conversion in sustained culture of warm-water fish in fresh, estuarine and marine waters. The control of diseases has been dependent on the use of therapeutics since the inception of...
Diversity of Prophage DNA Regions of Streptococcus agalactiae Clonal Lineages from Adults and Neonates with Invasive Infectious Disease
Salloum, Mazen; van der Mee-Marquet, Nathalie; Valentin-Domelier, Anne-Sophie; Quentin, Roland
The phylogenetic position and prophage DNA content of the genomes of 142 S. agalactiae (group-B streptococcus, GBS) isolates responsible for bacteremia and meningitis in adults and neonates were studied and compared. The distribution of the invasive isolates between the various serotypes, sequence types (STs) and clonal complexes (CCs) differed significantly between adult and neonatal isolates. Use of the neighbor-net algorithm with the PHI test revealed evidence for recombination in the population studied (PHI, P?=?2.01×10?6), and the recombination-mutation ratio (R/M) was 6?7. Nevertheless, the estimated R/M ratio differed between CCs. Analysis of the prophage DNA regions of the genomes of the isolates assigned 90% of the isolates to five major prophage DNA groups: A to E. The mean number of prophage DNA fragments amplified per isolate varied from 2.6 for the isolates of prophage DNA group E to 4.0 for the isolates of prophage DNA group C. The isolates from adults and neonates with invasive diseases were distributed differently between the various prophage DNA groups (P<0.00001). Group C prophage DNA fragments were found in 52% of adult invasive isolates, whereas 74% of neonatal invasive isolates had prophage DNA fragments of groups A and B. Differences in prophage DNA content were also found between serotypes, STs and CCs (P<0.00001). All the ST-1 and CC1 isolates, mostly of serotype V, belonged to the prophage DNA group C, whereas 84% of the ST-17 and CC17 isolates, all of serotype III, belonged to prophage DNA groups A and B. These data indicate that the transduction mechanisms, i.e., gene transfer from one bacterium to another by a bacteriophage, underlying genetic recombination in S. agalactiae species, are specific to each intraspecies lineage and population of strains responsible for invasive diseases in adults and neonates. PMID:21633509
Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes.
Flores, Anthony R; Galloway-Peńa, Jessica; Sahasrabhojane, Pranoti; Saldańa, Miguel; Yao, Hui; Su, Xiaoping; Ajami, Nadim J; Holder, Michael E; Petrosino, Joseph F; Thompson, Erika; Margarit Y Ros, Immaculada; Rosini, Roberto; Grandi, Guido; Horstmann, Nicola; Teatero, Sarah; McGeer, Allison; Fittipaldi, Nahuel; Rappuoli, Rino; Baker, Carol J; Shelburne, Samuel A
The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans. PMID:25941374
Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease
Beres, Stephen B.; Sesso, Ricardo; Pinto, Sergio Wyton L.; Hoe, Nancy P.; Porcella, Stephen F.; DeLeo, Frank R.; Musser, James M.
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis. PMID:18716664
Pyogenic brain abscess, a 15 year survey
Background Brain abscess is a potentially fatal disease. This study assesses clinical aspects of brain abscess in a large hospital cohort. Methods Retrospective review of adult patients with pyogenic brain abscess at Rigshospitalet University Hospital, Denmark between 1994 and 2009. Prognostic factors associated with Glasgow Outcome Score (GOS) (death, severe disability or vegetative state) were assessed by logistic regression. Results 102 patients were included. On admission, only 20% of patients had a triad of fever, headache and nausea, 39% had no fever, 26% had normal CRP and 49% had no leucocytosis. Median delay from symptom onset to antibiotic treatment was 7 days (range 0–97 days). Source of infection was contiguous in 36%, haematogenous in 28%, surgical or traumatic in 9% and unknown in 27% of cases. Abscess location did not accurately predict the portal of entry. 67% were treated by burr hole aspiration, 20% by craniotomy and 13% by antibiotics alone. Median duration of antibiotic treatment was 62 days. No cases of recurrent abscess were observed. At discharge 23% had GOS ?3. The 1-, 3- and 12-month mortality was 11%, 17% and 19%. Adverse outcome was associated with a low GCS at admission, presence of comorbidities and intraventricular rupture of abscess. Conclusions The clinical signs of brain abscess are unspecific, many patients presented without clear signs of infection and diagnosis and treatment were often delayed. Decreased GCS, presence of comorbidities and intraventricular rupture of brain abscess were associated with poor outcome. Brain abscess remains associated with considerable morbidity and mortality. PMID:23193986
Outbreak of Group A beta hemolytic Streptococcus pharyngitis in a Peruvian military facility, April 2012.
Ramos, Mariana; Valle, Ruben; Reaves, Eric J; Loayza, Luis; Gonzalez, Sofia; Bernal, Maria; Soto, Giselle; Hawksworth, Anthony W; Kasper, Matthew R; Tilley, Drake H; De Mattos, Carlos A; Brown, Jason R; Bausch, David G
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a common cause of acute pharyngitis as well as other diseases. Closed populations such as those living on military bases, nursing homes, and prisons are particularly vulnerable to GAS outbreaks due to crowding that facilitates person-to-person transmission. This report details a large outbreak of GAS pharyngitis at a Peruvian military training facility near Lima, Peru, in April 2012. Initial findings showed 145 cases. However, as the investigation continued it was revealed that some trainees may have concealed their illness to avoid real or perceived negative consequences of seeking medical care. A subsequent anonymous survey of all trainees revealed at least 383 cases of pharyngitis among the facility's 1,549 trainees and an attack rate of 34 percent among the 1,137 respondents. The epidemic curve revealed a pattern consistent with routine person-to-person transmission, although a point-source initiating event could not be excluded. Laboratory results showed GAS emm type 80.1 to be the culprit pathogen, an organism not commonly implicated in outbreaks of GAS in the Americas. Barious unique and illustrative features of outbreak investigation in military facilities and populations are discussed. PMID:23819536
Laminotomy with Continuous Irrigation in Patients with Pyogenic Spondylitis in Thoracic and Lumbar Spine
Kim, Sung-Hyun; Jang, Jae-Won; Seo, Bo-Ra; Kim, Tae-Sun; Kim, Soo-Han
Objective Pyogenic spondylitis often results in acute neurological deterioration requiring adequate surgical intervention and appropriate antibiotic treatment. The purpose of this study was to conduct an analysis of the clinical effect of continuous irrigation via laminotomy in a series of patients with pyogenic spondylitis in thoracic and lumbar spine. Methods The authors conducted a retrospective investigation of 31 consecutive patients with pyogenic thoracic and lumbar spondylitis who underwent continuous irrigation through laminotomy from 2004 to 2008. The study included 22 men and 9 women, ranging in age from 38 to 78 years (mean 58.1 years). The average follow-up duration was 13.4 months (range, 8-34 months). We performed debridement and abscess removal after simple laminotomy, and then washed out epidural and disc space using a continuous irrigation system. Broad spectrum antibiotics were administered empirically and changed according to the subsequent culture result. Clinical outcomes were based on the low back outcome scale (LBOS), visual analogue scale (VAS) score, and Frankel grade at the last follow-up. Radiological assessment involved plain radiographs, including functional views. Results Common predisposing factors included local injection for pain therapy, diabetes mellitus, chronic renal failure, and liver cirrhosis. Causative microorganisms were identified in 22 cases (70.9%) : Staphylococcus aureus and Streptococcus spp. were the main organisms. After surgery, LBOS, VAS score, and Frankel grade showed significant improvement in most patients. Spinal stability was maintained during the follow-up period, making secondary reconstructive surgery unnecessary for all patients, except one. Conclusion Simple laminotomy with continuous irrigation by insertion of a catheter into intervertebral disc space or epidural space was minimally invasive and effective in the treatment of pyogenic spondylitis. This procedure could be a beneficial treatment option in patients with thoracolumbar spondylitis combined with minimal or moderate destructive change of vertebrae. PMID:22200016
Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans
Background We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19?F and 23?F) of varying invasive disease potential. Results The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed. Conclusions Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform. PMID:23107513
Pyogenic liver abscess: an unusual cause.
Dinnoo, A; Barbier, L; Soubrane, O
A 60-year-old female patient was referred for a massive pyogenic liver abscess that had been initially treated with percutaneous drainage and antibiotics. CT-scan showed a foreign body in the hepatic pedicle, adjacent to the right portal vein: a fishbone. After 6 weeks of medical management with antibiotics, the foreign body was removed laparoscopically. The presence of a foreign body should be sought in cases of pyogenic liver abscess, especially if no other intra-abdominal cause has been found or if the abscess fails to resolve with medical treatment alone. PMID:25662871
Comparison of Pyogenic Spondylitis and Tuberculous Spondylitis
Pyogenic spondylitis and tuberculous spondylitis are common causes of spinal infection. It is difficult to differentiate tuberculous spondylitis and pyogenic spondylitis clinically and radiologically. Recently magnetic resonance imaging has been reported to be beneficial for early diagnosis and differential diagnosis of the spondylitis, and is being used extensively for diagnosis. However, the diagnosis must be considered in combination with corresponding changes in clinical manifestations, radiological findings, blood and tissue cultures and histopathological findings. Conservative treatments, including antimicrobial medications, are started initially. Surgical treatments, which include anterior or posterior approach, single-stage or two-stage surgery, with or without instrumentation, may be performed as indicated. PMID:24761207
Percutaneous Management of Pyogenic Liver Abscesses
Helenon, O.; Krachte, M.; Mathieu, D.; Vasile, N.; Rotman, N.
Twenty-four pyogenic liver abscesses have been treated during a six-year period percutaneously. Percutaneous management included percutaneous drainage and fine needle aspiration under ultrasound or CT scan guidance. Percutaneous management was successful in 92% of cases, and no further treatment was required in 91% of these. One patient died, giving a mortality rate of 4.1%. There were no complications related to this method. The authors conclude that percutaneous management of pyogenic liver abscesses should be attempted in all cases, since results compare favourably with surgical procedures. PMID:2487072
Group A streptococcus cell-associated pathogenic proteins as revealed by growth in hyaluronic acid-enriched media.
Zhang, Meng; McDonald, Fiona M; Sturrock, Shane S; Charnock, Simon J; Humphery-Smith, Ian; Black, Gary W
Group A streptococcus (GAS), also know as Streptococcus pyogenes, is a human pathogen and can cause several fatal invasive diseases such as necrotising fasciitis, the so-called flesh-eating disease, and toxic shock syndrome. The destruction of connective tissue and the hyaluronic acid (HA) therein, is a key element of GAS pathogenesis. We therefore propagated GAS in HA-enriched growth media in an attempt to create a simple biological system that could reflect some elements of GAS pathogenesis. Our results show that several recognised virulence factors were up-regulated in HA-enriched media, including the M1 protein, a collagen-like surface protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, which has been shown to play important roles in streptococcal pathogenesis. Interestingly, two hypothetical proteins of unknown function were also up-regulated and detailed bioinformatics analysis showed that at least one of these hypothetical proteins is likely to be involved in pathogenesis. It was therefore concluded that this simple biological system provided a valuable tool for the identification of potential GAS virulence factors. PMID:17407184
Ampicillin-sulbactam therapy for multiple pyogenic hepatic abscesses.
Zenon, G J; Cadle, R M; Hamill, R J
A patient with multiple, pyogenic hepatic abscesses is described, and the pathophysiology, etiologies, clinical and laboratory manifestations, and management of the disease are reviewed. A 55-year-old man with a history of ethanol abuse and pancreatitis developed fever, chills, general malaise, and right upper quadrant abdominal pain two weeks before hospitalization. Baseline laboratory and hematology results included serum albumin concentration, 3.2 g/dL; serum alkaline phosphatase concentration, 239 mIU/mL; total serum bilirubin concentration, 1.3 mg/dL; white blood cell count, 18,400/cu mm; red blood cell count, 4.7 million/cu mm; hemoglobin, 12.5 g/dL; and hematocrit, 38.8%. Abdominal ultrasound showed echo-free cavities throughout the hepatic parenchyma; abdominal computed-tomography (CT) scan showed hepatomegaly and multiple radiolucent spaces. CT-guided needle aspiration of a hepatic mass yielded purulent material that grew Fusobacterium necrophorum under anaerobic conditions. On day 7, the patient was started on i.v. ampicillin sodium-sulbactam sodium. A CT scan two weeks later showed a reduction in the number and sizes of abscesses. The patient continued i.v. therapy for one month, then was discharged on a regimen of p.o. amoxicillin trihydrate-clavulanate potassium. Hepatic abscesses are either amebic or pyogenic; the latter usually has a higher mortality. The etiologies of pyogenic hepatic abscesses include ascending cholangitis, portal vein bacteremia, systemic bacteremia, extension from a contiguous focus of infection, and trauma. Diagnosis is difficult and relies highly on clinical suspicion. Clinical symptoms include hepatomegaly, fever, chills, and malaise. Abnormal laboratory values include leukocytosis, anemia, and hypoalbuminemia. The abscesses are frequently polymicrobial; Escherichia coli is the most commonly isolated species. CT is the best radiological technique for diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2292177
Habitat, wildlife, and one health: Arcanobacterium pyogenes in Maryland and Upper Eastern Shore white-tailed deer populations
Turner, Melissa M.; DePerno, Christopher S.; Conner, Mark C.; Eyler, T. Brian; Lancia, Richard A.; Klaver, Robert W.; Stoskopf, Michael K.
Background Understanding the distribution of disease in wildlife is key to predicting the impact of emerging zoonotic one health concerns, especially for wildlife species with extensive human and livestock interfaces. The widespread distribution and complex interactions of white-tailed deer (Odocoileus virginianus) with humans suggest deer population health and management may have implications beyond stewardship of the animals. The intracranial abscessation suppurative meningitis (IASM) disease complex in deer has been linked to Arcanobacterium pyogenes, an under-diagnosed and often misdiagnosed organism considered commensal in domestic livestock but associated with serious disease in numerous species, including humans. Methods Our study used standard bacterial culture techniques to assess A. pyogenes prevalence among male deer sampled across six physiogeographic regions in Maryland and male and female deer in the Upper Eastern Shore under Traditional Deer Management (TDM) and Quality Deer Management (QDM), a management protocol that alters population demographics in favor of older male deer. Samples were collected from antler pedicles for males, the top of the head where pedicles would be if present for females, or the whole dorsal frontal area of the head for neonates. We collected nasal samples from all animals by swabbing the nasopharyngeal membranes. A gram stain and catalase test were conducted, and aerobic bacteria were identified to genus and species when possible. We evaluated the effect of region on whether deer carried A. pyogenes using Pearson's chi-square test with Yates' continuity correction. For the white-tailed deer management study, we tested whether site, age class and sex predisposed animals to carrying A. pyogenes using binary logistic regression. Results A. pyogenes was detected on deer in three of the six regions studied, and was common in only one region, the Upper Eastern Shore. In the Upper Eastern Shore, 45% and 66% of antler and nasal swabs from deer were positive for A. pyogenes, respectively. On the Upper Eastern Shore, prevalence of A. pyogenes cultured from deer did not differ between management areas, and was abundant among both sexes and across all age classes. No A. pyogenes was cultured from a small sample of neonates. Conclusion Our study indicates A. pyogenes may be carried widely among white-tailed deer regardless of sex or age class, but we found no evidence the pathogen is acquired in utero. The distribution of A. pyogenes across regions and concentration in a region with low livestock levels suggests the potential for localized endemicity of the organism and the possibility that deer may serve as a maintenance reservoir for an emerging one health concern. PMID:23930157
Identification of a Novel Virulence Determinant with Serum Opacification Activity in Streptococcus suis
Baums, Christoph G.; Kaim, Ute; Fulde, Marcus; Ramachandran, Girish; Goethe, Ralph; Valentin-Weigand, Peter
Streptococcus suis serotype 2 is a porcine and human pathogen with adhesive and invasive properties. In other streptococci, large surface-associated proteins (>100 kDa) of the MSCRAMM family (microbial surface components recognizing adhesive matrix molecules) are key players in interactions with host tissue. In this study, we identified a novel opacity factor of S. suis (OFS) with structural homology to members of the MSCRAMM family. The N-terminal region of OFS is homologous to the respective regions of fibronectin-binding protein A (FnBA) of Streptococcus dysgalactiae and the serum opacity factor (SOF) of Streptococcus pyogenes. Similar to these two proteins, the N-terminal domain of OFS opacified horse serum. Serum opacification activity was detectable in sodium dodecyl sulfate extracts of wild-type S. suis but not in extracts of isogenic ofs knockout mutants. Heterologous expression of OFS in Lactococcus lactis demonstrated that a high level of expression of OFS is sufficient to provide surface-associated serum opacification activity. Furthermore, serum opacification could be inhibited by an antiserum against recombinant OFS. The C-terminal repetitive sequence elements of OFS differed significantly from the respective repeat regions of FnBA and SOF as well as from the consensus sequence of the fibronectin-binding repeats of MSCRAMMs. Accordingly, fibronectin binding was not detectable in recombinant OFS. To investigate the putative function of OFS in the pathogenesis of invasive S. suis diseases, piglets were experimentally infected with an isogenic mutant strain in which the ofs gene had been knocked out by an in-frame deletion. The mutant was severely attenuated in virulence but not in colonization, demonstrating that OFS represents a novel virulence determinant of S. suis. PMID:17057090
Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis.
Baums, Christoph G; Kaim, Ute; Fulde, Marcus; Ramachandran, Girish; Goethe, Ralph; Valentin-Weigand, Peter
Streptococcus suis serotype 2 is a porcine and human pathogen with adhesive and invasive properties. In other streptococci, large surface-associated proteins (>100 kDa) of the MSCRAMM family (microbial surface components recognizing adhesive matrix molecules) are key players in interactions with host tissue. In this study, we identified a novel opacity factor of S. suis (OFS) with structural homology to members of the MSCRAMM family. The N-terminal region of OFS is homologous to the respective regions of fibronectin-binding protein A (FnBA) of Streptococcus dysgalactiae and the serum opacity factor (SOF) of Streptococcus pyogenes. Similar to these two proteins, the N-terminal domain of OFS opacified horse serum. Serum opacification activity was detectable in sodium dodecyl sulfate extracts of wild-type S. suis but not in extracts of isogenic ofs knockout mutants. Heterologous expression of OFS in Lactococcus lactis demonstrated that a high level of expression of OFS is sufficient to provide surface-associated serum opacification activity. Furthermore, serum opacification could be inhibited by an antiserum against recombinant OFS. The C-terminal repetitive sequence elements of OFS differed significantly from the respective repeat regions of FnBA and SOF as well as from the consensus sequence of the fibronectin-binding repeats of MSCRAMMs. Accordingly, fibronectin binding was not detectable in recombinant OFS. To investigate the putative function of OFS in the pathogenesis of invasive S. suis diseases, piglets were experimentally infected with an isogenic mutant strain in which the ofs gene had been knocked out by an in-frame deletion. The mutant was severely attenuated in virulence but not in colonization, demonstrating that OFS represents a novel virulence determinant of S. suis. PMID:17057090
21 CFR 866.3720 - Streptococcus spp. exo-enzyme reagents.
Code of Federal Regulations, 2010 CFR
...identify antibodies to Streptococcus spp. exoenzyme in serum. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Streptococcus and provides epidemiological information on these diseases. Pathogenic...
Genetic Determinants of Capsular Serotype K1 of Klebsiella pneumoniae Causing Primary Pyogenic Liver Abscess
Background. Primary pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae is an emerging infectious disease. Capsular serotype K1 and the magA gene have been reported to be associated with this disease. Methods. The prevalence of magA was determined by polymerase chain reaction (PCR). The sequences of the magA flanking region were completed by inverse PCR and direct sequencing. Serotyping was
Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis
Verhaegh, Suzanne J. C.; Flores, Anthony R.; van Belkum, Alex; Musser, James M.; Hays, John P.
Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (?4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (?4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence. PMID:23626831
Camel Streptococcus agalactiae populations are associated with specific disease complexes and acquired the tetracycline resistance gene tetM via a Tn916-like element
Camels are the most valuable livestock species in the Horn of Africa and play a pivotal role in the nutritional sustainability for millions of people. Their health status is therefore of utmost importance for the people living in this region. Streptococcus agalactiae, a Group B Streptococcus (GBS), is an important camel pathogen. Here we present the first epidemiological study based on genetic and phenotypic data from African camel derived GBS. Ninety-two GBS were characterized using multilocus sequence typing (MLST), capsular polysaccharide typing and in vitro antimicrobial susceptibility testing. We analysed the GBS using Bayesian linkage, phylogenetic and minimum spanning tree analyses and compared them with human GBS from East Africa in order to investigate the level of genetic exchange between GBS populations in the region. Camel GBS sequence types (STs) were distinct from other STs reported so far. We mapped specific STs and capsular types to major disease complexes caused by GBS. Widespread resistance (34%) to tetracycline was associated with acquisition of the tetM gene that is carried on a Tn916-like element, and observed primarily among GBS isolated from mastitis. The presence of tetM within different MLST clades suggests acquisition on multiple occasions. Wound infections and mastitis in camels associated with GBS are widespread and should ideally be treated with antimicrobials other than tetracycline in East Africa. PMID:24083845
Estimation of the invasive disease potential of Streptococcus pneumoniae in children by the use of direct capsular typing in clinical specimens.
del Amo, E; Selva, L; de Sevilla, M F; Ciruela, P; Brotons, P; Trivińo, M; Hernandez, S; Garcia-Garcia, J J; Dominguez, Á; Muńoz-Almagro, C
Traditionally, invasiveness indexes have been based on culture methods. We aimed to establish a new classification of the invasive disease potential of pneumococcal serotypes causing invasive pediatric disease in the era of conjugate vaccines in Catalonia, Spain, by adding capsular typing of Streptococcus pneumoniae in direct sample. Two samples of children attended at the University Hospital Sant Joan de Déu (Barcelona, Spain) between 2007 and 2011 were compared: a first sample of 358 children with invasive pneumococcal disease and a second sample of 402 pneumococcal nasopharyngeal carriers selected from 714 healthy children admitted for minor surgical procedures. The most common invasive serotypes were 1 (20.1 %, n?=?72), 19A (13.9 %, n?=?50), 3 (12.3 %, n?=?44), and 7FA (7.5 %, n?=?27), whereas the most common serotypes in carriage were 19A (8.7 %, n?=?38), 10FC33C (7.8 %, n?=?34), 6C (6.9 %, n?=?30), and 19FBC (5.5 %, n?=?24). We detected a rate of cocolonization of 26.4 % (n?=?89) among the 336 samples serotyped in the carriers population. Serotypes 1, 3, and 7FA were significantly associated with high invasiveness. Serotypes 6C, 10FC33C, 23A, 35B, 19FBC, 21, 11AD, 15BC, 23B, 34, and 6A were significantly associated with low invasiveness. Our results proved that the use of molecular techniques in direct sample for both the detection and the capsular identification of Streptococcus pneumoniae is very useful to obtain a more accurate calculation of the invasiveness of the different pneumococcal serotypes. PMID:25413925
Antimicrobial Resistance Profile and Genotypic Characteristics of Streptococcus suis Capsular Type 2 Isolated from Clinical Carrier Sows and Diseased Pigs in China
Zhang, Chunping; Zhang, Zhongqiu; Song, Li; Fan, Xuezheng; Wen, Fang; Xu, Shixin; Ning, Yibao
Streptococcus suis serotype 2 is an important zoonotic pathogen. Antimicrobial resistance phenotypes and genotypic characterizations of S. suis 2 from carrier sows and diseased pigs remain largely unknown. In this study, 96 swine S. suis type 2, 62 from healthy sows and 34 from diseased pigs, were analyzed. High frequency of tetracycline resistance was observed, followed by sulfonamides. The lowest resistance of S. suis 2 for ?-lactams supports their use as the primary antibiotics to treat the infection of serotype 2. In contrast, 35 of 37 S. suis 2 with MLSB phenotypes were isolated from healthy sows, mostly encoded by the ermB and/or the mefA genes. Significantly lower frequency of mrp+/epf+/sly+ was observed among serotype 2 from healthy sows compared to those from diseased pigs. Furthermore, isolates from diseased pigs showed more homogeneously genetic patterns, with most of them clustered in pulsotypes A and E. The data indicate the genetic complexity of S. suis 2 between herds and a close linkage among isolates from healthy sows and diseased pigs. Moreover, many factors, such as extensive use of tetracycline or diffusion of Tn916 with tetM, might have favored for the pathogenicity and widespread dissemination of S. suis serotype 2. PMID:26064892
Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012
Ramdani-Bouguessa, N.; Ziane, H.; Bekhoucha, S.; Guechi, Z.; Azzam, A.; Touati, D.; Naim, M.; Azrou, S.; Hamidi, M.; Mertani, A.; Laraba, A.; Annane, T.; Kermani, S.; Tazir, M.
Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria.
Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012.
Ramdani-Bouguessa, N; Ziane, H; Bekhoucha, S; Guechi, Z; Azzam, A; Touati, D; Naim, M; Azrou, S; Hamidi, M; Mertani, A; Laraba, A; Annane, T; Kermani, S; Tazir, M
Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria. PMID:26106481
Giant Pyogenic Granuloma in a Patient with Chronic Lymphocytic Leukemia
Plovanich, Molly; Tsibris, Hillary C.; Lian, Christine G.; Mostaghimi, Arash
Pyogenic granuloma, also known as lobular capillary hemangioma, is a common benign vascular proliferative lesion that can present at any age on the skin or mucous membranes. Most lesions do not exceed 2 cm, but there are a handful of giant cutaneous pyogenic granulomas that have been reported, often in individuals with underlying immune dysfunction. Here, we report the first giant pyogenic granuloma in a patient with a hematological malignancy, chronic lymphocytic leukemia. PMID:25408651
Infratentorial subdural empyemas mimicking pyogenic meningitis
Gupta, Anurag; Karanth, Suman S; Raja, A
Infratentorial subdural empyema is an extremely rare condition which unfortunately mimics pyogenic meningitis in 75% of cases. While an ill-planned lumbar puncture in these cases may be fatal, an inadvertent delay in treatment may be detrimental to the outcome for the patient. We present a case of a young boy with long standing history of chronic suppurative otitis media (CSOM) presenting with an infratentorial empyema with features suggestive of pyogenic meningitis. We also review the available literature to further define the condition in terms of clinical features, treatment options, and outcome. A misdiagnosis of this condition with failure to institute appropriate surgical intervention and antibiotic therapy is potentially life threatening. We highlight this rare condition which requires a high degree of suspicion especially in the presence of associated risk factors. PMID:23914110
Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.
Johnson, Abdul-Wahab B. R.; Adedoyin, Olanrewaju T.; Abdul-Karim, Aishat A.; Olanrewaju, Abdul-Waheed I.
The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID:17722674
... information on enabling JavaScript. Pneumococcal Disease Skip Content Marketing Share this: Main Content Area Streptococcus Pneumoniae Streptococcus pneumoniae are bacteria frequently found in the upper respiratory tract of healthy children and adults. These bacteria, however, can also cause ...
Single and Multiple Pyogenic Liver Abscesses: Clinical Course, Etiology, and Results of Treatment
Fong-Fu Chou; Shyr-Ming Sheen-Chen; Yaw-Sen Chen; Mao-Chan Chen
. A total of 483 patients with pyogenic\\u000a liver abscess during the years 1986 to June 1995 were studied at Chang\\u000a Gung Memorial Hospital in Kaohsiung: 343 were a single abscess and 140\\u000a were multiple abscesses. Males were predominantly affected by this\\u000a disease. Abdominal pain was more frequent with the single abscess than\\u000a with multiple abscesses, and jaundice was more
Characterization and protective immunogenicity of the SzM protein of Streptococcus zooepidemicus NC78 from a clonal outbreak of equine respiratory disease.
Velineni, Sridhar; Timoney, John F
Streptococcus zooepidemicus of Lancefield group C is a highly variable tonsillar and mucosal commensal that usually is associated with opportunistic infections of the respiratory tract of vertebrate hosts. More-virulent clones have caused epizootics of severe respiratory disease in dogs and horses. The virulence factors of these strains are poorly understood. The antiphagocytic protein SeM is a major virulence factor and protective antigen of Streptococcus equi, a clonal biovar of an ancestral S. zooepidemicus strain. Although the genome of S. zooepidemicus strain H70, an equine isolate, contains a partial homolog (szm) of sem, expression of the gene has not been documented. We have identified and characterized SzM from an encapsulated S. zooepidemicus strain from an epizootic of equine respiratory disease in New Caledonia. The SzM protein of strain NC78 (SzM(NC78)) has a predicted predominantly alpha-helical fibrillar structure with an LPSTG cell surface anchor motif and resistance to hot acid. A putative binding site for plasminogen is present in the B repeat region, the sequence of which shares homology with repeats of the plasminogen binding proteins of human group C and G streptococci. Equine plasminogen is activated in a dose-dependent manner by recombinant SzM(NC78). Only 23.20 and 25.46% DNA homology is shared with SeM proteins of S. equi strains CF32 and 4047, respectively, and homology ranges from 19.60 to 54.70% for SzM proteins of other S. zooepidemicus strains. As expected, SzM(NC78) reacted with convalescent-phase sera from horses with respiratory disease associated with strains of S. zooepidemicus. SzM(NC78) resembles SeM in binding equine fibrinogen and eliciting strong protective antibody responses in mice. Sera of vaccinated mice opsonized S. zooepidemicus strains NC78 and W60, the SzM protein of which shared partial amino acid homology with SzM(NC78). We conclude that SzM is a protective antigen of NC78; it was strongly reactive with serum antibodies from horses during recovery from S. zooepidemicus-associated respiratory disease. PMID:23740925
A Second Tylosin Resistance Determinant, Erm B, in Arcanobacterium pyogenes
B. Helen Jost; Hien T. Trinh; J. Glenn Songer; Stephen J. Billington
Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of livestock, is also a pathogen associated with a variety of infections. In livestock, A. pyogenes is exposed to antimicrobial agents used for prophylaxis and therapy, notably tylosin, a macrolide used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Many, but not all, tylosin-resistant A.
CT in pyogenic osteomyelitis of the spine
Kattapuram, S.V.; Phillips, W.C.; Boyd, R.
Six patients with bacteriologically proven pyogenic osteomyelitis of the spine were followed serially with computed tomography (CT). Initial evaluation of the involved vertebral bodies and adjacent soft tissues showed a drop in CT numbers when compared to normal cancellous bone and soft tissues. A soft-tissue mass was seen in all cases. After appropriate antibiotic therapy, all six patients showed an increase in bone density and a diminution of the soft-tissue mass (p < 0.05). Five of the six patients showed a further decrease in soft-tissue CT numbers.
Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging
Adatepe, M.H.; Powell, O.M.; Isaacs, G.H.; Nichols, K.; Cefola, R.
Hematogenous pyogenic vertebral osteomyelitis (HPVO) continues to be a diagnostic problem for clinicians due to nonspecific presentation of the disease (1,2). We reviewed our experience of the last 10 years to determine the diagnostic usefulness of radionuclide bone studies in this disease. We found 15 patients whose primary diagnosis was HPVO. Of the 15 patients, 12 had (99mTc)MDP bone scans which were all positive. Five of the 12 patients had positive (/sup 67/Ga)citrate scans and one patient with chronic active HPVO had negative /sup 67/Ga and (/sup 111/In)WBC bone images. At the same time, three patients' spine x-rays and one patient's CT scan of the vertebra were normal. Additionally, in three patients spine x-rays were interpreted as consistent with degenerative joint disease that contributed to the delay of the diagnosis. We conclude that when HPVO is suspected an abnormal (99mTc)MDP bone image increases the probability of the disease, even if the x-rays and CT scans of the spine are normal. An abnormal /sup 67/Ga image following an abnormal 99mTc bone image increases the specificity of the diagnosis. Normal (99mTc)MDP and (/sup 67/Ga)citrate bone images of the vertebra virtually exclude the diagnosis of HPVO.
Distinct Structural Features of the Peroxide Response Regulator from Group A Streptococcus Drive DNA Binding
Hammel, Michal; Nix, Jay C.; Tseng, Hsiao-Ling; Tsou, Chih-Cheng; Fei, Chun-Hsien; Chiou, Huo-Sheng; Jeng, U-Ser; Lin, Yee-Shin; Chuang, Woei-Jer; Wu, Jiunn-Jong; Wang, Shuying
Group A streptococcus (GAS, Streptococcus pyogenes) is a strict human pathogen that causes severe, invasive diseases. GAS does not produce catalase, but has an ability to resist killing by reactive oxygen species (ROS) through novel mechanisms. The peroxide response regulator (PerR), a member of ferric uptake regulator (Fur) family, plays a key role for GAS to cope with oxidative stress by regulating the expression of multiple genes. Our previous studies have found that expression of an iron-binding protein, Dpr, is under the direct control of PerR. To elucidate the molecular interactions of PerR with its cognate promoter, we have carried out structural studies on PerR and PerR-DNA complex. By combining crystallography and small-angle X-ray scattering (SAXS), we confirmed that the determined PerR crystal structure reflects its conformation in solution. Through mutagenesis and biochemical analysis, we have identified DNA-binding residues suggesting that PerR binds to the dpr promoter at the per box through a winged-helix motif. Furthermore, we have performed SAXS analysis and resolved the molecular architecture of PerR-DNA complex, in which two 30 bp DNA fragments wrap around two PerR homodimers by interacting with the adjacent positively-charged winged-helix motifs. Overall, we provide structural insights into molecular recognition of DNA by PerR and define the hollow structural arrangement of PerR-30bpDNA complex, which displays a unique topology distinct from currently proposed DNA-binding models for Fur family regulators. PMID:24586487
Manganese Homeostasis in Group A Streptococcus Is Critical for Resistance to Oxidative Stress and Virulence
Turner, Andrew G.; Ong, Cheryl-lynn Y.; Gillen, Christine M.; Davies, Mark R.; West, Nicholas P.; McEwan, Alastair G.
ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448?mntE mutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448?mntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observed ex vivo reduction in virulence. In the presence of manganese and hydrogen peroxide, 5448?mntE mutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448?mntE-?perR double mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence. PMID:25805729
Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae
Kong, Il Gyu; Sato, Ayuko; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E.; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari
To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513
21 CFR 866.3740 - Streptococcus spp. serological reagents.
Code of Federal Regulations, 2013 CFR
...spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Streptococcus and provides epidemiological information on these diseases. Pathogenic...
21 CFR 866.3740 - Streptococcus spp. serological reagents.
Code of Federal Regulations, 2010 CFR
...spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Streptococcus and provides epidemiological information on these diseases. Pathogenic...
Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences
Nasser, Waleed; Beres, Stephen B.; Olsen, Randall J.; Dean, Melissa A.; Rice, Kelsey A.; Long, S. Wesley; Kristinsson, Karl G.; Gottfredsson, Magnus; Vuopio, Jaana; Raisanen, Kati; Caugant, Dominique A.; Steinbakk, Martin; Low, Donald E.; McGeer, Allison; Darenberg, Jessica; Henriques-Normark, Birgitta; Van Beneden, Chris A.; Hoffmann, Steen; Musser, James M.
We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD+-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide. PMID:24733896
Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.
Nasser, Waleed; Beres, Stephen B; Olsen, Randall J; Dean, Melissa A; Rice, Kelsey A; Long, S Wesley; Kristinsson, Karl G; Gottfredsson, Magnus; Vuopio, Jaana; Raisanen, Kati; Caugant, Dominique A; Steinbakk, Martin; Low, Donald E; McGeer, Allison; Darenberg, Jessica; Henriques-Normark, Birgitta; Van Beneden, Chris A; Hoffmann, Steen; Musser, James M
We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide. PMID:24733896
Comparison ofGen-Probe GroupA Streptococcus Direct Test withCulture forDiagnosing Streptococcal Pharyngitis
TheGroupAStreptococcus Direct Test(GP-ST test; Gen-Probe, Inc., SanDiego, Calif.) wascompared with culture forthedetection ofStreptococcus pyogenes fromthroat swabsof767patients withpharyngitis. Swabs weretested bytheGP-STtest after inoculating a5%sheep bloodagar(SBA) plate. SBAplates wereincubated at35°Cinroomairfor72h.SBAplates withnoevidence ofbeta-hemolytic colonies after 18to24h of incubation weresubcultured bytaking aswipe across theprimary inoculum fromtheSBAplate toanagar selective forStreptococcus spp.Inalow-prevalence (11.9%) population andincomparison withthenumberof positive cultures detected bythe72-hsingle-culture method(SBAplate method), theGP-STtesthada sensitivity of88.6%, aspecificity
Quantitative susceptibility of Streptococcus suis strains isolated from diseased pigs in seven European countries to antimicrobial agents licensed in veterinary medicine.
Wisselink, Henk J; Veldman, Kees T; Van den Eede, Chris; Salmon, Sarah A; Mevius, Dik J
The susceptibility of Streptococcus suis strains (n=384) isolated from diseased pigs in seven European countries to 10 antimicrobial agents was determined. For that purpose a microbroth dilution method was used according to CLSI recommendations. The following antimicrobial agents were tested: ceftiofur, cefquinome, enrofloxacin, florfenicol, gentamicin, penicillin, spectinomycin, tetracycline, tilmicosin and trimethoprim/sulphamethoxazole. Using breakpoints established by CLSI for veterinary pathogens, all strains were susceptible to ceftiofur, florfenicol, enrofloxacin and penicillin. MIC-90 values of these antibiotics were < or = 0.03, 0.5, 2 and < or = 0.13 microg/mL, respectively. A low degree of resistance was observed for gentamicin (1.3%), spectinomycin (3.6%) and trimethoprim/sulphamethoxazole (6.0%). MIC-90 values of these antibiotics were 8, 16 and 2 microg/mL, respectively. A high level of resistance was observed for tetracycline (75.1%). A MIC-90 value of 64 microg/mL was found for this antibiotic. Serotype-associated differences in MIC-90 values were observed for tetracycline, tilmicosin and trimethoprim/suphamethoxazole. PMID:16387456
Human Streptococcus agalactiae isolate in Nile tilapia (Oreochromis niloticus)
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus agalactiae, the Lancefield group B Streptococcus (GBS), long recognized as a mammalian pathogen, is an emerging pathogen to fish. We show that a GBS serotype Ia, multilocus sequence type ST-7 isolate from a human neonatal meningitis clinical case causes disease signs and mortality in N...
Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease
Stephen B. Beres; Ricardo Sesso; Sergio Wyton L. Pinto; Nancy P. Hoe; Stephen F. Porcella; Frank R. Deleo; James M. Musser; Niyaz Ahmed
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group
[Pathognomonic magnetic resonance imaging (MRI) finding of fluid-fluid level in pyogenic ventriculitis: two case reports].
Hatakeyama, Masahiro; Kanazawa, Masato; Ishihara, Ayako; Tanabe, Yoshinari; Shimohata, Takayoshi; Nishizawa, Masatoyo
Pyogenic ventriculitis is an uncommon and potentially fatal central nervous system infection. Delayed treatment due to non specific clinical symptoms may lead to an unfavorable outcome. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of pyogenic ventriculitis. We describe two patients with pyogenic ventriculitis presenting with a pathognomonic MRI finding. The first patient, a 77-year-old female, developed high fever and consciousness disturbance. MR images revealed hyperintense lesions with a fluid-fluid level in the bilateral lateral ventricles on diffusion-weighted images (DWIs) and hypointense lesions on T2-weighted images (T2WIs). MR images also revealed findings of left otitis media. The second patient, a 63-year-old male, who had a past history of multiple myeloma and had received chemotherapy, developed high fever and left hemiparesis. MR images revealed a hyperintense lesion with a fluid-fluid level in the right lateral ventricle on DWIs and a hypointense lesion on T2WIs, multiple ring-enhancing lesions on gadolinium enhanced T1-weighted images, and pontine infarction on DWIs. Chest computed tomography revealed an infiltrative shadow in the lower lobe of the left lung. On the basis of MRI findings, both patients were diagnosed as having pyogenic ventriculitis and were administered high-dose meropenem intravenously. The second patient was also administered sulfamethoxazole-trimethoprim orally. Intraventricular abnormalities disappeared and the patients achieved complete remission after the antibacterial treatment. Intraventricular hyperintense lesions on DWIs and hypointense ones on T2WIs with a fluid-fluid level is a pathognomonic finding of pyogenic ventriculitis and has not been previously reported in other diseases. Recognition of the characteristic MRI features and initiation of high-dose and appropriate antibiotics in an early stage may lead to a favorable outcome of the disease. PMID:25283828
Bactericidal effect of extracts and metabolites of Robinia pseudoacacia L. on Streptococcus mutans and Porphyromonas gingivalis causing dental plaque and periodontal inflammatory diseases.
Patra, Jayanta Kumar; Kim, Eun Sil; Oh, Kyounghee; Kim, Hyeon-Jeong; Dhakal, Radhika; Kim, Yangseon; Baek, Kwang-Hyun
The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus mutans and Porphyromonas gingivalis, which cause periodontal inflammatory diseases and dental caries. The present study was conducted to evaluate the antibacterial potential of extracts of Robinia pseudoacacia and its different fractions, as well as some of its natural compounds against oral pathogens and a nonpathogenic reference bacteria, Escherichia coli. The antibacterial activity of the crude extract and the solvent fractions (hexane, chloroform, ethyl acetate and butanol) of R. pseudoacacia were evaluated against S. mutans, P. gingivalis and E. coli DH5? by standard micro-assay procedure using conventional sterile polystyrene microplates. The results showed that the crude extract was more active against P. gingivalis (100% growth inhibition) than against S. mutans (73% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fractions were active against P. gingivalis, with 91 and 97% growth inhibition, respectively, at 0.2 mg/mL. None of seven natural compounds found in R. pseudoacacia exerted an antibacterial effect on P. gingivalis; however, fisetin and myricetin at 8 µg/mL inhibited the growth of S. mutans by 81% and 86%, respectively. The crude extract of R. pseudoacacia possesses bioactive compounds that could completely control the growth of P. gingivalis. The antibiotic activities of the hexane and chloroform fractions suggest that the active compounds are hydrophobic in nature. The results indicate the effectiveness of the plant in clinical applications for the treatment of dental plaque and periodontal inflammatory diseases and its potential use as disinfectant for various surgical and orthodontic appliances. PMID:25856062
Tonsillopharyngitis caused by foodborne group A streptococcus: a prison-based outbreak.
Levy, Michael; Johnson, Christine G; Kraa, Ed
An outbreak of tonsillopharyngitis due to Streptococcus pyogenes occurred among inmates of a rural correctional center in New South Wales, Australia. A total of 72 (28%) of 256 inmates became ill in December 1999. S. pyogenes type M-75, T-25, which was opacity factor positive, was isolated from throat swab specimens obtained from 5 of 57 inmates with primary cases and from 4 of 15 inmates with secondary cases, as well as from specimens obtained from the hand wounds and throat of one of the food handlers. The consumption of curried egg rolls (i.e., curried egg salad sandwiches) was the most likely association with this outbreak. The presumed source of the food contamination was the food handler who had infected hand wounds. There has been only one other outbreak of streptococcal pharyngitis reported from a prison. Other outbreaks have been reported from military bases, nursing homes, and community picnics. PMID:12522749
SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion
Gallotta, Marilena; Gancitano, Giovanni; Pietrocola, Giampiero; Mora, Marirosa; Pezzicoli, Alfredo; Tuscano, Giovanna; Chiarot, Emiliano; Nardi-Dei, Vincenzo; Taddei, Anna Rita; Rindi, Simonetta; Speziale, Pietro; Soriani, Marco; Bensi, Giuliano
Group A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of the spy0269 gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interact in vitro with the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cells in vitro and that Lactococcus lactis expressing Spy0269 on its cell surface could adhere to mammalian cells in vitro and to mice nasal mucosa in vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (Streptococcus pyogenes Adhesion and Division protein). PMID:24778116
Protein Array Profiling of Tic Patient Sera Reveals a Broad Range and Enhanced Immune Response against Group A Streptococcus Antigens
Bombaci, Mauro; Grifantini, Renata; Mora, Marirosa; Reguzzi, Valerio; Petracca, Roberto; Meoni, Eva; Balloni, Sergio; Zingaretti, Chiara; Falugi, Fabiana; Manetti, Andrea G. O.; Margarit, Immaculada; Musser, James M.; Cardona, Francesco; Orefici, Graziella; Grandi, Guido; Bensi, Giuliano
The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen-dependent induction of autoantibodies in susceptible individuals may be involved the occurrence of tic disorders. PMID:19623252
SpyAD, a moonlighting protein of group A Streptococcus contributing to bacterial division and host cell adhesion.
Gallotta, Marilena; Gancitano, Giovanni; Pietrocola, Giampiero; Mora, Marirosa; Pezzicoli, Alfredo; Tuscano, Giovanna; Chiarot, Emiliano; Nardi-Dei, Vincenzo; Taddei, Anna Rita; Rindi, Simonetta; Speziale, Pietro; Soriani, Marco; Grandi, Guido; Margarit, Immaculada; Bensi, Giuliano
Group A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of the spy0269 gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interact in vitro with the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cells in vitro and that Lactococcus lactis expressing Spy0269 on its cell surface could adhere to mammalian cells in vitro and to mice nasal mucosa in vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (Streptococcus pyogenes Adhesion and Division protein). PMID:24778116
Evidence for niche adaptation in the genome of the bovine pathogen Streptococcus uberis
Ward, Philip N; Holden, Matthew TG; Leigh, James A; Lennard, Nicola; Bignell, Alexandra; Barron, Andy; Clark, Louise; Quail, Michael A; Woodward, John; Barrell, Bart G; Egan, Sharon A; Field, Terence R; Maskell, Duncan; Kehoe, Michael; Dowson, Christopher G; Chanter, Neil; Whatmore, Adrian M; Bentley, Stephen D; Parkhill, Julian
Background Streptococcus uberis, a Gram positive bacterial pathogen responsible for a significant proportion of bovine mastitis in commercial dairy herds, colonises multiple body sites of the cow including the gut, genital tract and mammary gland. Comparative analysis of the complete genome sequence of S. uberis strain 0140J was undertaken to help elucidate the biology of this effective bovine pathogen. Results The genome revealed 1,825 predicted coding sequences (CDSs) of which 62 were identified as pseudogenes or gene fragments. Comparisons with related pyogenic streptococci identified a conserved core (40%) of orthologous CDSs. Intriguingly, S. uberis 0140J displayed a lower number of mobile genetic elements when compared with other pyogenic streptococci, however bacteriophage-derived islands and a putative genomic island were identified. Comparative genomics analysis revealed most similarity to the genomes of Streptococcus agalactiae and Streptococcus equi subsp. zooepidemicus. In contrast, streptococcal orthologs were not identified for 11% of the CDSs, indicating either unique retention of ancestral sequence, or acquisition of sequence from alternative sources. Functions including transport, catabolism, regulation and CDSs encoding cell envelope proteins were over-represented in this unique gene set; a limited array of putative virulence CDSs were identified. Conclusion S. uberis utilises nutritional flexibility derived from a diversity of metabolic options to successfully occupy a discrete ecological niche. The features observed in S. uberis are strongly suggestive of an opportunistic pathogen adapted to challenging and changing environmental parameters. PMID:19175920
Insight into the Evolution of the Histidine Triad Protein (HTP) Family in Streptococcus
Pan, Xiu-Zhen; Wang, Bin; Chen, Jian-Qun
The Histidine Triad Proteins (HTPs), also known as Pht proteins in Streptococcus pneumoniae, constitute a family of surface-exposed proteins that exist in many pathogenic streptococcal species. Although many studies have revealed the importance of HTPs in streptococcal physiology and pathogenicity, little is known about their origin and evolution. In this study, after identifying all htp homologs from 105 streptococcal genomes representing 38 different species/subspecies, we analyzed their domain structures, positions in genome, and most importantly, their evolutionary histories. By further projecting this information onto the streptococcal phylogeny, we made several major findings. First, htp genes originated earlier than the Streptococcus genus and gene-loss events have occurred among three streptococcal groups, resulting in the absence of the htp gene in the Bovis, Mutans and Salivarius groups. Second, the copy number of htp genes in other groups of Streptococcus is variable, ranging from one to four functional copies. Third, both phylogenetic evidence and domain structure analyses support the division of two htp subfamilies, designated as htp I and htp II. Although present mainly in the pyogenic group and in Streptococcus suis, htp II members are distinct from htp I due to the presence of an additional leucine-rich-repeat domain at the C-terminus. Finally, htp genes exhibit a faster nucleotide substitution rate than do housekeeping genes. Specifically, the regions outside the HTP domains are under strong positive selection. This distinct evolutionary pattern likely helped Streptococcus to easily escape from recognition by host immunity. PMID:23527301
Changing trends in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive diseases in Central Thailand, 2009–2012
Phongsamart, Wanatpreeya; Srifeungfung, Somporn; Chatsuwan, Tanittha; Nunthapisud, Pongpun; Treerauthaweeraphong, Vipa; Rungnobhakhun, Pimpha; Sricharoenchai, Sirintip; Chokephaibulkit, Kulkanya
To describe the trends in serotype distribution and antimicrobial susceptibility of S. pneumoniae causing invasive pneumococcal diseases (IPD) we tested 238 pneumococci isolates from normally sterile sites between 2009 and 2012 and compared these findings with previous data collected within our network. Serotyping was performed for 15 serotypes contained in the 7-,10-, 13-, and experimental 15-valent pneumococcal conjugate vaccines (PCV). The most common serotypes found were 6B (13.9%), 19A (12.6%), 14 (8.0%), 18C (5.9%), and 6A (3.8%); and 39.9% were non-PCV15 serotypes. One of 81 patients with available data had breakthrough infection with vaccine serotype (19F). There was a significant increase of serotype 19A among children ?5 years (5.6% in 2000–2009 vs 18.3% in 2009–2012, P = 0.003). The all-age serotype coverage was 36.4%, 41.5%, 59.3%, and 59.7% for PCV7, PCV10, PCV13, and PCV 15, respectively. The corresponding coverage in children ?5 years were 46.4%, 48.8%, 73.2%, and 73.2% respectively. High susceptibilities to penicillin (89.7%), cefotaxime (95.7%), cefditoren (90.2% by Spanish breakpoints), ofloxacin (97.9%), and levofloxacin (100%), but low to cefdinir (50.0%), cefditoren (45.1% by US-FDA breakpoints), macrolides (<50%), clindamycin (67.7%), tetracycline (41.4%), and trimethoprim-sulfamethoxazole (32.4%) were observed. Serotype 19A was less susceptible to penicillin (80.0 vs 91.2%, P = 0.046), cefditoren (66.7 vs 95.5% by Spanish breakpoints, P = 0.004), and tetracycline (9.1 vs 45.5%, P = 0.024) than non-19A isolates. These data emphasize the need for continued surveillance to monitor changes in serotypes as well as antimicrobial susceptibilities in order to guide strategies for prevention and treatment. PMID:25424794
Characterization of Isolates of Streptococcus agalactiae from Diseased Farmed and Wild Marine Fish from the U.S. Gulf Coast, Latin America, and Thailand.
Soto, Esteban; Wang, Rui; Wiles, Judy; Baumgartner, Wes; Green, Christopher; Plumb, John; Hawke, John
We examined Lancefield serogroup B Streptococcus isolates recovered from diseased, cultured hybrid Striped Bass (Striped Bass Morone saxatilis × White Bass M. chrysops) and wild and cultured Gulf Killifish Fundulus grandis from coastal waters of the U.S. Gulf of Mexico (Gulf coast) and compared those isolates to strains from tilapias Oreochromis spp. reared in Mississippi, Thailand, Ecuador, and Honduras and to the original Gulf coast strain identified by Plumb et al. ( 1974 ). The isolates were subjected to phylogenetic, biochemical, and antibiotic susceptibility analyses. Genetic analysis was performed using partial sequence comparison of (1) the 16S ribosomal RNA (rRNA) gene; (2) the sipA gene, which encodes a surface immunogenic protein; (3) the cspA gene, which encodes a cell surface-associated protein; and (4) the secY gene, which encodes components of a general protein secretion pathway. Phylogenies inferred from sipA, secY, and cspA gene sequence comparisons were more discriminating than that inferred from the 16S rRNA gene sequence comparison. The U.S. Gulf coast strains showed a high degree of similarity to strains from South America and Central America and belonged to a unique group that can be distinguished from other group B streptococci. In agreement with the molecular findings, biochemical and antimicrobial resistance analyses demonstrated that the isolates recovered from the U.S. Gulf coast and Latin America were more similar to each other than to isolates from Thailand. Three laboratory challenge methods for inducing streptococcosis in Gulf Killifish were evaluated-intraperitoneal (IP) injection, immersion (IMM), and immersion plus abrasion (IMMA)-using serial dilutions of S. agalactiae isolate LADL 97-151, a representative U.S. Gulf coast strain. The dose that was lethal to 50% of test fish by 14 d postchallenge was approximately 2 CFU/fish via IP injection. In contrast, the fish that were challenged via IMM or IMMA presented cumulative mortality less than 40% by 14 d postchallenge. Received July 31, 2014; accepted March 11, 2015. PMID:26030196
Clonal diversity of Streptococcus pyogenes within some M-types revealed by multilocus enzyme electrophoresis.
Haase, A. M.; Melder, A.; Mathews, J. D.; Kemp, D. J.; Adams, M.
Twenty-two reference isolates and 30 local isolates of group A Streptococci were classified into 36 electrophoretic types (ET) on the basis of allozyme variation at 27 enzyme loci. Local isolates were characterized by a high frequency of M-non typable strains. M-type and ET were more closely associated in local isolates from an endemically-infected population; nevertheless, amongst the local isolates there were also strains of the same ET type with different M-types. A possible explanation is that genetic exchange between strains may introduce different M-types into strains of defined ET when these are exposed to strong selection in the presence of heavy loads of infection. In contrast to the reported clustering of strains associated with toxic shock-like syndrome into two closely related ET clones, we found no relationship of ET phenotype to acute poststreptococcal glomerulonephritis or rheumatic fever. PMID:7995355
Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease.
Burns, E H; Marciel, A M; Musser, J M
Human umbilical vein endothelial cells (HUVECs) were used to gain insight into the molecular mechanism whereby the major extracellular protease from group A streptococci damages host tissue. HUVECs exposed to streptococcal cysteine protease (SCP) for various times exhibited cytopathic effect and cell detachment from the culture vessel. Gelatin substrate zymography showed that a time- and concentration-dependent increase in the level of activity of an approximately 66-kDa gelatinase occurred in culture medium taken from cells exposed to enzymatically active SCP. This gelatinase comigrated in gelatin zymograms with the activated form of purified recombinant matrix metalloprotease 2 (MMP-2) and had type IV collagenase activity. In contrast, medium taken from cells exposed to inactivated (boiled) SCP and cells exposed to SCP inhibited by treatment with N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethyl ketone lacked the 66-kDa gelatinase. Appearance of the 66-kDa gelatinase activity was also prevented by 1,10-phenanthroline, a zinc chelator and MMP inhibitor. Inasmuch as proteolytically active SCP is required for the emergence of this gelatinase and MMP activation occurs by proteolytic processing, the 66-kDa gelatinase may be a proteolytic cleavage product of a latent MMP expressed extracellularly by HUVECs. Direct SCP treatment of culture supernatant taken from HUVECs not exposed to SCP also produced the 66-kDa gelatinase. The data show that SCP activates an MMP produced by human endothelial cells, a process that may contribute to endothelial cell damage, tissue destruction, and hemodynamic derangement observed in some patients with severe, invasive group A streptococcal infection. PMID:8890235
Targeted Quantitative Analysis of Streptococcus pyogenes Virulence Factors by Multiple Reaction Monitoring
Vinzenz Lange; Johan A. Malmstrom; John Didion; Nichole L. King; Bjorn P. Johansson; Juliane Schafer; Jonathan Rameseder; Chee-Hong Wong; Eric W. Deutsch; Mi-Youn Brusniak; Peter Buhlmann; Lars Bjorck; Bruno Domon; R. Aebersold
In many studies, particularly in the field of systems biol- ogy, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the imple- mentation of
Differentiation between Tuberculous Spondylitis and Pyogenic Spondylitis on MR Imaging
Park, Jong-Han; Shin, Hye-Seon; Park, Jong Tae; Kim, Tae Young
Objective The objective of this study was to compare the magnetic resonance (MR) imaging of tuberculous spondylitis with pyogenic spondylitis. Methods MR images of the spines of 41 patients with infectious spondylitis at our institution over 8-years of period were retrospectively reviewed. Eighteen patients with infective spondylitis were excluded because their results on the marrow biopsy and culture were negative. MR imaging findings in 6 patients with tuberculous spondylitis (3 male, 3 female) were compared with those of 17 patients (10 male, 7 female) with pyogenic spondylitis. Results Two MR imaging findings were statiscally significant in differentiating the tuberculous spondylitis from pyogenic spondylitis: a well defined paraspinal abnormal signal and a thin and smooth abscess wall. There were no significant differences in the following MR imaging findings: paraspinal abscess or intraosseous abscess, subligamentous spread to three or more vertebra, involvement of multiple vertebra, hyperintense signal on T2-weighted images, heterogenous low signal on T1-weighted images, involvement of posterior element, epidural extension, involvement of intervertebral disk, disk space narrowing, rim enhancement of the abscess, skip lesion, and endplate destruction. Conclusion MR imaging is an appropriate modality for differentiation of tuberculous spondylitis from pyogenic spondylitis.
Diagnosis of hematogenous pyogenic vertebral osteomyelitis by magnetic resonance imaging
S. P. Meyers; S. N. Wiener
The clinical information and imaging data from 27 patients with hematogenous pyogenic vertebral osteomyelitis were reviewed. All patients had roentgenographic and magnetic resonance imaging examinations. Seventeen patients had computed tomograms; 17 had technetium Tc 99m medronate bone scans; and seven had gallium citrate Ga 67 scans. Magnetic resonance imaging, when used as a part of the initial radiologic evaluation, detected
Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: Characterization of \\
The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distin- guished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three
Mga is sufficient to activate transcription in vitro of sof-sfbX and other Mga-regulated virulence genes in the group A Streptococcus.
Almengor, Audry C; Walters, Matthew S; McIver, Kevin S
The group A streptococcus (GAS), or Streptococcus pyogenes, is a strict human pathogen of medical significance, causing infections ranging from pharyngitis (strep throat) to necrotizing fasciitis (flesh-eating disease). Several virulence genes that encode factors important for colonization, internalization, and immune evasion are under the control of the multiple gene regulator of the GAS, or Mga. Mga functions as a DNA-binding protein that interacts with sites both proximal (Pemm and PscpA) and distal (PsclA) to the start of transcription for the genes that it regulates. The genes encoding serum opacity factor, sof, and a novel fibronectin-binding protein, sfbX, are cotranscribed and represent two uncharacterized Mga-regulated virulence genes in the GAS. Analysis of the promoter region of sof-sfbX identified a putative Mga-binding site 278 bp upstream of the regulated start of transcription as determined by primer extension. Electrophoretic mobility shift assays demonstrated that Mga is able to bind specifically to the single distal site in a fashion similar to the previously characterized PsclA. In order to better understand the events that take place at this and other Mga-regulated promoters, an in vitro transcription assay was established. Using this assay, we showed that Mga is sufficient to activate transcription in vitro for Mga-regulated promoters containing both proximal (Pemm) and distal (PsclA and Psof-sfbX) binding sites. These results indicate that additional factors are not required for Mga-specific activation at diverse promoters in vitro, although they do not rule out the potential influence of other components on the Mga virulence regulon in vivo. PMID:16513733
Experimentally induced orchitis associated with Arcanobacterium pyogenes: clinical, ultrasonographic, seminological and pathological features.
Gouletsou, P G; Fthenakis, G C; Cripps, P J; Papaioannou, N; Lainas, T; Psalla, D; Amiridis, G S
The objectives of this study were to describe the features of experimentally induced orchitis associated with Arcanobacterium pyogenes and confirm the pathogenicity of the organism for the ovine testicle. One testicle of each of nine rams was inoculated with 1.3 +/- 10(4) colony-forming-units of an A. pyogenes isolate and regular clinical, ultrasonographic, bacteriological and seminological examinations were carried out up to 204 days after challenge. The rams were sequentially euthanatized 3, 6, 9, 18, 30, 50, 71, 113 and 204 days after challenge and a gross- and histopathological examination of their testicles was performed. All rams developed clinical orchitis and general signs. The initial ultrasonographic findings were changes of size and echogenicity of the genitalia, whilst in the long-standing phase they were wider appearance of the mediastinum testis, presence of hyperechogenic foci, changes of echogenicity of the genitalia and increased echogenicity of the scrotum and tunics. The following changes in semen evaluation parametres were recorded: the pH, the percentage of dead sperms, the percentage of abnormal sperms and the number of nonsperm round cells increased, whilst the mass motility, the individual motility and the sperm concentration decreased; the following sperm defects were observed: misshapen or piriform heads, sperms with coiled tails, sperms without tail and sperms with proximal cytoplasmic droplet; at the early stages neutrophils were the prevailing nonsperm round cell type, later the proportion of immature germ cells increased and in the long-standing phase there were enlogated spermatids and leucocytes; it is noteworthy that semen evaluation parametres were restored to normal at the late stages of the disease. A. pyogenes was consistently isolated from the semen samples after challenge, as well as from the dissected genitalia. The salient post-mortem findings were: initially, subcutaneous oedema, fluid into the vaginal cavity, congested and distended vessels, increased size of the genitalia and a hard dark area inside the testicles; subsequently, there were changes of size of the genitalia, thickening of scrotum and tunics and presence of fibrin on the testicular surface; in the long-standing phase of the disorder, there were induration of scrotum and tunics with adhesion between the tunics and discolouration of the surface of the genitalia. The prominent histopathological changes were observed in the inoculated testicles; milder changes were seen in the respective epididymides; interstitial oedema, diffuse neutrophilic infiltration and extravasation were observed in the early stages after challenge; lymphocytic infiltration with concurrent fibrosis, mineralization and inspissation of the tubular elements of the seminiferous tubules and presence of vacuolated Sertoli cells were seen later; finally, regeneration of the epithelium and presence of Sertoli cells and spermatogonia with various degrees of spermatogenic activity were evident. These findings, allied to the isolation of A. pyogenes from field cases of ovine orchitis, provide clear evidence that A. pyogenes is pathogenic for the ovine genitalia; however, the mechanisms of transition of the organism from commensal to pathogenic state are not clear. It is also noteworthy that some degree of fertility was restored in the late stages of the disorder. Ultrasonography appeared to be useful for the diagnosis of intra-scrotal abnormalities, especially during investigation of the long-standing stage of the disease, after clinical findings have subsided. PMID:15325557
Phylogenomics and the dynamic genome evolution of the genus Streptococcus.
Richards, Vincent P; Palmer, Sara R; Pavinski Bitar, Paulina D; Qin, Xiang; Weinstock, George M; Highlander, Sarah K; Town, Christopher D; Burne, Robert A; Stanhope, Michael J
The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group. PMID:24625962
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus iniae is among the most important emergent pathogens that affects many fish species worldwide, especially in warm-water regions. In marine and freshwater systems, this Gram-positive bacterium causes significant economic losses, estimated at hundreds of millions of dollars annually. Inf...
Two Novel Superantigens Found in Both Group A and Group C Streptococcus
Proft, Thomas; Webb, Phillip D.; Handley, Vanessa; Fraser, John D.
Two novel streptococcal superantigen genes (speLSe and speMSe) were identified from the Streptococcus equi genome database at the Sanger Center. Genotyping of 8 S. equi isolates and 40 Streptococcus pyogenes isolates resulted in the detection of the orthologous genes speL and speM in a restricted number of S. pyogenes isolates (15 and 5%, respectively). Surprisingly, the novel superantigen genes could not be found in any of the analyzed S. equi isolates. The results suggest that both genes are located on a mobile element that enables gene transfer between individual isolates and between streptococci from different Lancefield groups. S. equi pyrogenic exotoxin L (SPE-LSe)/streptococcal pyrogenic exotoxin L (SPE-L) and SPE-MSe/SPE-M are most closely related to SMEZ, SPE-C, SPE-G, and SPE-J, but build a separate branch within this group. Recombinant SPE-L (rSPE-L) and rSPE-M were highly mitogenic for human peripheral blood lymphocytes, with half-maximum responses at 1 and 10 pg/ml, respectively. The results from competitive binding experiments suggest that both proteins bind major histocompatibility complex class II at the ?-chain, but not at the ?-chain. The most common targets for both toxins were human V?1.1 expressing T cells. Seroconversion against SPE-L and SPE-M was observed in healthy blood donors, suggesting that the toxins are expressed in vivo. Interestingly, the speL gene is highly associated with S. pyogenes M89, a serotype that is linked to acute rheumatic fever in New Zealand. PMID:12595453
Identification of a Second Arcanobacterium pyogenes Neuraminidase and Involvement of Neuraminidase Activity in Host Cell Adhesion
B. Helen Jost; J. Glenn Songer; Stephen J. Billington
Arcanobacterium pyogenes, a common inhabitant of the upper respiratory and urogenital tracts of econom- ically important animals, such as cattle and swine, is also an opportunistic pathogen associated with suppu- rative infections in these animals. A. pyogenes expresses neuraminidase activity encoded by the nanH gene, and previously, construction of a nanH mutant of A. pyogenes BBR1 indicated that a second
Periungual pyogenic granulomas due to topical tazarotene for nail psoriasis.
Piraccini, B M; Venturi, M; Patrizi, A
Tazarotene is a topically-applied, receptor-selective retinoid that has been shown to modulate several major pathogenic factors of psoriasis. Adverse effects are those of topical application of retinoids, the most common being mild to moderate burning, itching, stinging, and erythema, due to mild to moderate local skin irritation. While pyogenic granuloma-like lesions are a well recognized side effects of systemic retinoids, to our knowledge in the literature there is only one reported case of pyogenic granuloma (PG) following topical application of tazarotene for scalp psoriasis. In this paper we report 2 cases of periungual PGs following application of topical tazarotene and we present a review of the literature. PMID:24819765
Diagnosis of hematogenous pyogenic vertebral osteomyelitis by magnetic resonance imaging
Meyers, S.P.; Wiener, S.N. (Mt Sinai Medical Center, Cleveland, OH (USA))
The clinical information and imaging data from 27 patients with hematogenous pyogenic vertebral osteomyelitis were reviewed. All patients had roentgenographic and magnetic resonance imaging examinations. Seventeen patients had computed tomograms; 17 had technetium Tc 99m medronate bone scans; and seven had gallium citrate Ga 67 scans. Magnetic resonance imaging, when used as a part of the initial radiologic evaluation, detected abnormalities consistent with osteomyelitis in all 27 patients. Magnetic resonance imaging also demonstrated paravertebral and/or epidural extension of infection in 14 patients, including seven patients who had neurologic signs of lower-extremity weakness. Roentgenograms, computed tomograms, technetium bone scans, and gallium scans had findings suggestive of the diagnosis in 48%, 65%, 71%, and 86% of the patients, respectively. We recommend magnetic resonance imaging as an important and perhaps critical imaging modality for detection of pyogenic vertebral osteomyelitis.
Surgical treatment of pyogenic vertebral osteomyelitis with spinal instrumentation
Chen, Wei-Hua; Jiang, Lei-Sheng
Pyogenic vertebral osteomyelitis responds well to conservative treatment at early stage, but more complicated and advanced conditions, including mechanical spinal instability, epidural abscess formation, neurologic deficits, and refractoriness to antibiotic therapy, usually require surgical intervention. The subject of using metallic implants in the setting of infection remains controversial, although more and more surgeons acknowledge that instrumentation can help the body to combat the infection rather than to interfere with it. The combination of radical debridement and instrumentation has lots of merits such as, restoration and maintenance of the sagittal alignment of the spine, stabilization of the spinal column and reduction of bed rest period. This issue must be viewed in the context of the overall and detailed health conditions of the subjecting patient. We think the culprit for the recurrence of infection is not the implants itself, but is the compromised general health condition of the patients. In this review, we focus on surgical treatment of pyogenic vertebral osteomyelitis with special attention to the role of spinal instrumentation in the presence of pyogenic infection. PMID:17106664
Atlantoaxial Subluxation after Pyogenic Spondylitis around the Odontoid Process
Hasegawa, Atsushi; Yagi, Mitsuru; Takemitsu, Masakazu; Machida, Masafumi; Asazuma, Takashi; Ichimura, Shoichi
Study Design. A case report and review of the literature. Objective. The aim of this study was to describe the conservative management of pyogenic spondylitis around the odontoid process. Summary of Background Data. Atlantoaxial subluxation after pyogenic spondylitis is rare. The therapeutic approach to infection of the upper cervical spine is controversial. Methods. Medical chart and radiological images of a 76-year-old male patient were retrospectively reviewed. Radiography revealed atlantoaxial subluxation, and an abscess was seen around the odontoid process on magnetic resonance images. Intravenous antibiotics and a halo vest were used to treat the patient. We then observed the patient's conservative treatment course. Results. C-reactive protein levels returned to normal 4 weeks after administration of the intravenous antibiotics. The patient's muscle weakness also completely recovered 8 weeks after administration of the intravenous antibiotics. Because the patient was able to walk without any support, surgical treatment was not necessary. Conclusions. Pyogenic spondylitis of the upper cervical spine is a rare manifestation. Surgical or conservative treatment must be selected carefully based on the patient's symptoms. If early diagnosis and treatment can be provided to the patients, conservative treatment can be achieved.
Dominance of multidrug-resistant Denmark(14)-32 (ST230) clone among Streptococcus pneumoniae serotype 19A isolates causing pneumococcal disease in Bulgaria from 1992 to 2013.
Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio
A pneumococcal conjugate vaccine (PCV10) was introduced in Bulgarian national immunization program since April 2010. Clonal composition based on pulsed-field gel electrophoresis and multilocus sequence typing genotyping of 52 serotype 19A Streptococcus pneumoniae isolates was analyzed. These were invasive and respiratory isolates collected between 1992 and 2013 from both children (78.8% <5 years) and adults with pneumococcal infections. Multidrug resistance was found in 82.7% of all 19A isolates. The most prevalent genotype (63.5%) among serotype 19A pneumococcal strains was the multidrug-resistant clonal complex CC230, which is a capsular switched variant of the Denmark(14)-32 (ST230) global clone. The most frequent sequence type (ST) was ST230 (48.1%) and together with four other closely related STs (15.4%), belonging to ST1611, ST276, ST7466, and ST2013, which were single- and double-locus variants; they were included in the main CC230. The disappearance of highly drug-resistant ST663 clone and emergence of new clones as CC320 and CC199 was also observed among the rest 19A isolates. A comparison of clonal composition between invasive and noninvasive isolates did not show a great genetic diversity among both kinds of isolates. Continuous surveillance of serotype 19A population following the introduction of PCV10 is essential to evaluate the impact of the vaccine on the epidemiology of this serotype. PMID:25080213
Profusely bleeding oral pyogenic granuloma in a teenage girl
Singh, Rajeev Kumar; Kaushal, Ambrish; Kumar, Rakesh; Pandey, Ramesh Kumar
Pyogenic granuloma (PG) is a kind of inflammatory hyperplastic soft tissue lesion of the oral cavity. The lesion, however, is not related to infection and arise as a reactive growth in response to various stimuli. It has a very high vascularity because of the presence of numerous prominent capillaries. The lesion has a bleeding tendency, even after a minor traumatic episode, such as during mastication. Bleeding may be at times very severe and difficult to control. We present the case of a profusely bleeding young PG in a young teenage child. PMID:23486345
?-Galactosidase of Streptococcus lactis
Citti, J. E.; Sandine, W. E.; Elliker, P. R.
Citti, J. E. (Oregon State University, Corvallis), W. E. Sandine, and P. R. Elliker. ?-Galactosidase of Streptococcus lactis. J. Bacteriol. 89:937–942. 1965.—Synthesis of ?-galactosidase by several strains of Streptococcus lactis was induced by lactose. The rate of hydrolysis of o-nitrophenyl-?-d-galactopyranoside was used to measure enzyme activity. The enzyme of all but one strain was unstable when whole cells were sonic-treated or treated with toluene; the enzyme of one strain of S. lactis was stable to these treatments, which resulted in at least a fivefold increase in activity over that found in whole cells. The optimal assay conditions for toluene-treated cells of this strain involved incubation at 37 C in pH 7.0 sodium phosphate buffer. Lactose was the most effective inducer of enzyme synthesis. Methyl-?-d-thiogalactopyranoside, isopropyl-?-d-thiogalactopyranoside, and galactose were also inducers of the enzyme, but were not as effective as lactose. Melibiose, maltose, and calcium lactobionate were poor inducers of enzyme synthesis. Exogenously supplied glucose repressed enzyme synthesis. The means of control of induced ?-galactosidase synthesis in S. lactis was similar to that in Escherichia coli. PMID:14276118
The Transforming Streptococcus Pneumoniae in the 21st Century
Li-Min Huang
Streptococcus pneumoniae, an important pathogen causing sepsis, sinusitis, otitis media, bacterial meningitis and bacterial pneumonia, results in global morbidity and mortality each year. The burden of pneumococcal disease is highest in chil- dren and the elderly. Treatment of pneumococcal infection has been hampered by the complexity of the host immune response. In recent decades, the increase of S. pneumoniae strains'
Plants used in Guatemala for the treatment of respiratory diseases. 1. Screening of 68 plants against gram-positive bacteria.
Caceres, A; Alvarez, A V; Ovando, A E; Samayoa, B E
Respiratory ailments are important causes of morbidity and mortality in developing countries. Ethnobotanical surveys and literature reviews conducted in Guatemala during 1986-88 showed that 234 plants from 75 families, most of them of American origin, have been used for the treatment of respiratory ailments. Three Gram-positive bacteria causing respiratory infections (Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes) were used to screen 68 of the most commonly used plants for activity. Twenty-eight of these (41.2%) inhibited the growth of one or more of the bacteria tested. Staphylococcus aureus was inhibited by 18 of the plant extracts, while 7 extracts were effective against Streptococcus pyogenes. Plants of American origin which exhibited antibacterial activity were: Gnaphalium viscosum, Lippia alba, Lippia dulcis, Physalis philadelphica, Satureja brownei, Solanum nigrescens and Tagetes lucida. These preliminary in vitro results provide scientific basis for the use of these plants against bacterial respiratory infections. PMID:2023428
Gas-Forming Pyogenic Liver Abscess with Septic Shock
Ishaq, Muhammad K.; Jones, Kellie R.
The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its ?-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens.
Gas-Forming Pyogenic Liver Abscess with Septic Shock.
Khan, Muhammad S; Ishaq, Muhammad K; Jones, Kellie R
The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its ?-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens. PMID:26090240
Redundant Group A Streptococcus Signaling Peptides Exhibit Unique Activation Potentials
LaSarre, Breah; Chang, Jennifer C.
All bacterial quorum sensing (QS) systems are based on the production, secretion, and detection of small signaling molecules. Gram-positive bacteria typically use small peptides as QS effectors, and each QS circuit generally requires the interaction of a single signaling molecule with a single receptor protein. The recently described Rgg2 and Rgg3 (Rgg2/3) regulatory circuit of Streptococcus pyogenes (group A streptococcus [GAS]) is one of only a few QS circuits known to utilize multiple signaling peptides. In this system, two distinct, endogenously produced peptide pheromones (SHP2 and SHP3) both function to activate the QS circuit. The aim of this study was to further define the roles of SHP2 and SHP3 in activation of the Rgg2/3 QS system, specifically with regard to shp gene identity and dosage. Results from our studies using transcriptional reporters and isogenic GAS mutants demonstrate that shp gene dosage does contribute to Rgg2/3 system induction, as decreased gene dosage results in decreased or absent induction. Beyond this, however, data indicate that the shp genes possess distinct potentials for supporting system activation, with shp3 more readily able to support system activation than shp2. Studies using synthetic peptides and shp gene mutants indicate that the disparate activities of endogenous SHPs are due to production, rather than signaling, differences and are conferred by the N-terminal regions rather than the C-terminal signaling regions of the peptides. These data provide evidence that the N-terminal, noneffector sequences of SHP pheromones influence their production efficiencies and thereby the relative activation potentials of endogenous SHPs. PMID:23873915
A New Alkaline pH-Adjusted Medium Enhances Detection of ?-Hemolytic Streptococci by Minimizing Bacterial Interference Due to Streptococcus salivarius
Dierksen, Karen P.; Ragland, Nancy L.; Tagg, John R.
A new selective medium (CNA-P) that reduces or eliminates the inhibitory activity of bacteriocin-producing Streptococcus salivarius against ?-hemolytic streptococci has been developed and compared with sheep blood agar (SBA) for the sensitive detection of small numbers of ?-hemolytic streptococci in clinical specimens. CNA-P has as its basis a commercial medium (Difco Columbia CNA agar) supplemented with 5% (vol/vol) sheep blood, and the CNA is further modified by addition of 100 mM PIPES buffer [piperazine-N,N?-bis(2-ethanesulfonic acid)] (pH 7.5) to maintain cultures at an alkaline pH during incubation. CNA-P was shown to inhibit the production and/or release of four different types of S. salivarius bacteriocins or bacteriocin-like inhibitory molecules. The efficacies of CNA-P and SBA for detection of ?-hemolytic streptococci in 1,352 pharyngeal samples from 376 children were compared. The ?-hemolytic streptococcal isolates recovered from the samples included 314 group A (S. pyogenes), 61 group G, 33 group B, and 5 group C streptococci. Of 314 samples that yielded S. pyogenes, 300 were positive on CNA-P (96%) and 264 (86%) were positive on SBA. A significantly greater number of S. pyogenes isolates from these samples were recovered only on CNA-P (50 of 314) compared with the number of isolates recovered only on SBA (14 of 314). In addition, the degree of positivity, a measure of the total numbers of S. pyogenes isolates on the plate, was significantly higher on CNA-P than on SBA (2.40 versus 2.07; P < 0.001). Interestingly, CNA-P was also found to enhance the hemolytic activity of streptolysin O, allowing detection of streptolysin S-deficient S. pyogenes strains which might otherwise go undetected on SBA and other isolation media. PMID:10655361
Group A Streptococcal Infections
... NIAID clinical studies on ClinicalTrials.gov . Related Links? Bacterial Infections Emerging and Re-emerging Infectious Diseases National Library ... Protocols for Surveillance of Acute Diseases Caused by Streptococcus pyogenes : Pharyngitis, Impetigo, and Invasive Diseases (PDF). The following ...
Laser: A Powerful Tool for Treatment of Pyogenic Granuloma
Rai, Shalu; Kaur, Mandeep; Bhatnagar, Puneet
Lasers have opened a new door for the treatment of various disorders. Treatment of soft tissue intraoral mucosal growth by laser has profound effect on the patient acceptability taking the functional and aesthetic factor into consideration. The patient is able to get the outdoor treatment without the phobia of local anaesthetic and is out of the clinic in few minutes in contrast to the traditional method of surgical excision. Very few cases have been reported in literature regarding treatment of mucosal growth by soft tissue lasers. We present a case of recurrent pyogenic granuloma in a patient treated with an alternative approach, that is, diode laser, without the use of anaesthesia, sutures, anti-inflammatory drugs, or analgesics. The diagnosis of this lesion is equally important for correct treatment planning. PMID:21976910
[Pyogenic infections of the skin and skin appendages].
Schumpelick, V; Bertram, P
In Germany more than 120,000 soft tissue infections are treated in hospital per year. Articles about soft tissue infections caused by Strept. pyogenes, presented in the lay press as "flesh-eating bacteria", accentuate this picture. Among these soft tissue infections, necrotising fasciitis and the associated "toxic shock syndrome" and "toxic shock-like syndrome" remain a challenge to the surgeon. The most important role of surgery is to achieve the right diagnosis and introduce definitive therapy in time. Central to surgical therapy is immediate incision and open drainage. Our own experience in animal models underlines the important role of abscess pressure and physicochemical parameters in the "abscess compartment" for systemic spread. Based on this pathophysiological background, the traditional "ubi pus ibi evacua" has lost nothing of its importance. PMID:9574189
Pyogenic Granuloma of the Sigmoid Colon causing Intussusception in an Infant
Garofalo, Salvatore; Mostert, Michael; Morra, Isabella; Cortese, Maria Grazia; Mussa, Alessandro; Canesi, Mario; Carbonaro, Giulia; Cerrina, Alessia; Ferrero, Luisa; Cussa, Davide; Schleef, Jurgen
Pyogenic granuloma is a benign vascular tumor that may affect the gastrointestinal tract. This report describes a rare case of sigmoid-colon pyogenic granuloma in a 4-month-old boy causing intussusception. Resection and anastomosis were curative. The mother had history of high dose of progesterone exposure during initial weeks of conception for vaginal bleeding. This may point towards etiology of the lesion.
Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice
Aoife M. Roche; Samantha J. King; Jeffrey N. Weiser
Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneu- monia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another
Variation in the Presence of Neuraminidase Genes among Streptococcus pneumoniae Isolates with Identical Sequence Types
Melinda M. Pettigrew; Kristopher P. Fennie; Matthew P. York; Janeen Daniels; Faryal Ghaffar
Streptococcus pneumoniae frequently colonizes the upper respiratory tract of young children and is an important cause of otitis media and invasive disease. Carriage is more common than disease, yet the genetic factors that predispose a given clone for disease are not known. The relationship between capsule type, genetic background, and virulence is complex, and important questions remain regarding how pneumococcal
Multilocus Sequence Analysis of Streptococcus canis Confirms the Zoonotic Origin of Human Infections and Reveals Genetic Exchange with Streptococcus dysgalactiae subsp. equisimilis
Pinho, M. D.; Matos, S. C.; Pomba, C.; Lübke-Becker, A.; Wieler, L. H.; Preziuso, S.; Melo-Cristino, J.
Streptococcus canis is an animal pathogen that occasionally causes human infections. Isolates recovered from infections of animals (n = 78, recovered from 2000 to 2010 in three European countries, mainly from house pets) and humans (n = 7, recovered from 2006 to 2010 in Portugal) were identified by phenotypic and genotypic methods and characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and emm typing. S. canis isolates presented considerable variability in biochemical profiles and 16S rRNA. Resistance to antimicrobial agents was low, with the most significant being tet(M)- and tet(O)-mediated tetracycline resistance. MLST analysis revealed a polyclonal structure of the S. canis population causing infections, where the same genetic lineages were found infecting house pets and humans and were disseminated in distinct geographic locations. Phylogenetic analysis indicated that S. canis was a divergent taxon of the sister species Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis and found evidence of acquisition of genetic material by S. canis from S. dysgalactiae subsp. equisimilis. PFGE confirmed the MLST findings, further strengthening the similarity between animal and human isolates. The presence of emm-like genes was restricted to a few isolates and correlated with some MLST-based genetic lineages, but none of the human isolates could be emm typed. Our data show that S. canis isolates recovered from house pets and humans constitute a single population and demonstrate that isolates belonging to the main genetic lineages identified have the ability to infect the human host, providing strong evidence for the zoonotic nature of S. canis infection. PMID:23345291
Antibacterial effects of Traditional Chinese Medicine monomers against Streptococcus pneumoniae via inhibiting pneumococcal histidine kinase (VicK)
Zhang, Shuai; Wang, Jianmin; Xu, Wenchun; Liu, Yusi; Wang, Wei; Wu, Kaifeng; Wang, Zhe; Zhang, Xuemei
Two-component systems (TCSs) have the potential to be an effective target of the antimicrobials, and thus received much attention in recent years. VicK/VicR is one of TCSs in Streptococcus pneumoniae (S. pneumoniae), which is essential for pneumococcal survival. We have previously obtained several Traditional Chinese Medicine monomers using a computer-based screening. In this study, either alone or in combination with penicillin, their antimicrobial activities were evaluated based on in vivo and in vitro assays. The results showed that the MICs of 5?-(Methylthio)-5?-deoxyadenosine, octanal 2, 4-dinitrophenylhydrazone, deoxyshikonin, kavahin, and dodecyl gallate against S. pneumoniae were 37.1, 38.5, 17, 68.5, and 21 ?g/mL, respectively. Time-killing assays showed that these compounds elicited bactericidal effects against S. pneumoniae D39 strain, which led to a 6-log reduction in CFU after exposure to compounds at four times of the MIC for 24 h. The five compounds inhibited the growth of Streptococcus pyogenes, Streptococcus mitis, Streptococcus mutans or Streptococcus pseudopneumoniae, meanwhile, deoxyshikonin and dodecyl gallate displayed strong inhibitory activities against Staphylococcus aureus. These compounds showed no obvious cytotoxicity effects on Vero cells. Survival time of the mice infected by S. pneumoniae strains was prolonged by the treatment with the compounds. Importantly, all of the five compounds exerted antimicrobial effects against multidrug-resistant clinical strains of S. pneumoniae. Moreover, even at sub-MIC concentration, they inhibited cell division and biofilm formation. The five compounds all have enhancement effect on penicillin. Deoxyshikonin and dodecyl gallate showed significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and effectively reduced nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes. In addition, the two compounds also showed synergic antimicrobial activity with erythromycin and tetracycline. Taken together, our results suggest that these novel VicK inhibitors may be promising compounds against the pneumococcus, including penicillin-resistant strains. PMID:26042111
Crystal Structure of Streptococcus pyogenes Csn2 Reveals Calcium-Dependent Conformational Changes in Its Tertiary and Quaternary Structure
Yoon Koo; Du-kyo Jung; Euiyoung Bae
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute a microbial immune system against invading genetic elements, such as plasmids and phages. Csn2 is an Nmeni subtype-specific Cas protein, and was suggested to function in the adaptation process, during which parts of foreign nucleic acids are integrated into the host microbial genome to enable immunity against future
Monoarthrite ŕ Streptococcus pyogenes dans les suites d'une septoplastie : intéręt de la décontamination nasale en préopératoire
S. Gardes; M. Hellot; S. Tringali; J.-P. Larbre; F. Biron; G. Llorca; R. Girard
The nasal septoplasty is a very current intervention in otorhinolaryngology surgery. The infectious complications of this intervention are rare and mostly mild. We report here the case of a patient hospitalized in ambulatory surgery within a fracture of the nose with luxation of the septum in the nasal fossa. This patient was operated for a reduction of this fracture with
Combined Contributions of Streptolysin O and Streptolysin S to Virulence of Serotype M5 Streptococcus pyogenes Strain Manfredo
Michael C. Fontaine; Jeong Jin Lee; Michael A. Kehoe
Streptolysin O (SLO) and streptolysin S (SLS) are potent cytolytic toxins produced by almost all clinical isolates of group A streptococci (GAS). Allele-replacement mutagenesis was used to construct nonpolar (in-frame) deletion mutations in the slo and sagB genes of the serotype M5 GAS strain Manfredo, producing isogenic single and double SLO- and SLS-defective mutants. In contrast to recent reports on
Phenotypic characteristics and virulence genotypes of Trueperella (Arcanobacterium) pyogenes strains isolated from European bison (Bison bonasus).
Rzewuska, Magdalena; Stefa?ska, Ilona; Osi?ska, Barbara; Kizerwetter-?wida, Magdalena; Chrobak, Dorota; Kaba, Jaros?aw; Bielecki, Wojciech
Trueperella (Arcanobacterium) pyogenes is an opportunistic animal pathogen, which in European bison is associated with different suppurative infections mainly of the urogenital tract. Little is known about the virulence of this bacterium and about the pathogenesis of infections. The main objective of this study was to determine phenotypic properties and virulence genotypes of the twenty-five T. pyogenes strains isolated from lesions in various tissues of free-living European bison. Classical bacteriological methods were used for phenotypic characterization. Genes encoding seven known and putative virulence factors of T. pyogenes were detected by PCR technique. Analysis of 16S rDNA partial sequences was performed to establish phylogenetic relationships of the isolated strains. All isolates showed typical morphological features of T. pyogenes and variable biochemical activity. Most of them displayed a strong positive effect in synergistic CAMP test. For all isolates the 16S rRNA gene partial sequence was identical to that of the T. pyogenes reference strain. All isolates carried the plo and fimA genes, while the nanH, nanP, cbpA, fimC and fimG genes were present in 40, 44, 12, 88 and 24% of the isolates, respectively. The T. pyogenes strains isolated from European bison represented various phenotypes and virulence genotypes, but there was no association between the investigated properties of the bacteria and the type of anatomopathological lesions from which they were isolated. These results indicate that the studied virulence factors of T. pyogenes are not significant determinants of the localization and type of infection caused by this bacterium. PMID:22658663
Bilateral acute pyogenic conjunctivitis with iritis induced by unilateral topical application of bacterial peptidoglycan muramyl dipeptide in adult rabbits.
Langford, Marlyn P; Foreman, Bridgett D; Srur, Lana; Ganley, James P; Redens, Thomas B
The factors responsible for the conjunctivitis and iritis associated with acute ocular infection and post enteric inflammatory disease are not fully known. The pro-inflammatory activity of unilateral topical application of muramyl dipeptide (MDP; the smallest bio-active Gram-positive and Gram-negative bacterial cell wall component) was investigated in adult rabbits. The resultant bilateral conjunctivitis/iritis and pyogenic responses were characterized. Bilateral symptoms were graded by slit lamp examinations; tear fluid, Schirmer tests (tear production), blood and aqueous humor (AH) samples were obtained from MDP-treated and untreated rabbits. MDP concentration, gamma-glutamyltranspeptidase activity (GGT; key enzyme in glutathione recapture, xenobiotic detoxification, eicosanoid synthesis and neutrophil function), protein concentration, and tear cell density, cytology, and immunofluorescent antibody reactivity to GGT and calreticulin (CRT; MDP-binding protein) were determined. MDP was cleared from ipsilateral tears and serum by 6 h, but was undetected in mock-treated contralateral tears. Bilateral signs of acute transient pyogenic conjunctivitis, characterized by tearing, lid edema, conjunctival hyperemia, chemosis and leukocytic infiltrate with iritis (erythema and aqueous flare) were detected. Milder symptoms occurred in the mock-treated contralateral eyes. Bilateral symptoms, tear production, tear protein, GGT activity, and mucopurulent discharge (containing up to 2.5-5.0 × 10(6) cells/mL) were elevated 4-8 h post MDP and resolved to near pre-treatment levels by 24 h. Tear GGT activity and protein levels were higher in MDP-treated and mock-treated contralateral eyes than in eyes of untreated adult rabbits (p's < 0.001). Elevated tear GGT activity was associated with histopathology and increased vascular and epithelial permeability to serum protein, GGT-positive epithelia cells, macrophages and heterophils. Repeat MDP applications induced recurrent induction and resolution patterns of bilateral conjunctivitis/iritis and tear GGT activity, but ipsilateral GGT responses were lower. The results suggest unilateral topical MDP application to adult rabbit eyes induces a bilateral acute pyogenic conjunctivitis/iritis (PCI) characterized by increased vascular and epithelial permeability similar to acute bacterial conjunctivitis in man. The detection of CRT/GGT positive heterophils in tears suggests efferocytosis (phagocytosis of dead/dying cells). Tear GGT activity may be a useful means to quantify MDP-induced toxicity and extraocular inflammation. PMID:24135297
The effect of vaccination on Streptococcus pneumoniae resistance
Eugene Leibovitz; Pediatric Infectious
Following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV-7) in the routine immunization schedule of\\u000a US children, the morbidity and mortality associated with Streptococcus pneumoniae infections have changed considerably. Post-licensure data from the United States have confirmed that PCV-7 has significantly\\u000a decreased the incidence of vaccine-type susceptible and antibiotic-resistant invasive pneumococcal diseases, community-acquired\\u000a respiratory infections, and nasopharyngeal colonization in
Molecular characterization of an Australian serotype 1 Streptococcus pneumoniae outbreak.
Staples, M; Graham, R M A; Jennison, A V; Ariotti, L; Hicks, V; Cook, H; Krause, V; Giele, C; Smith, H V
Serotype 1 Streptococcus pneumoniae is a cause of invasive pneumococcal disease (IPD) worldwide and has been associated with IPD outbreaks, while carriage is rarely detected in healthy adults or children. This study details an Australian multi-state and territory outbreak of serotype 1 S. pneumoniae IPD between 2010 and 2012. Molecular characterization demonstrated the outbreak was largely due to the clonal expansion of sequence type 306, MLVA type 261 S. pneumoniae serotype 1. PMID:24666470
Population structure of Streptococcus oralis
Thuy Do; Keith A. Jolley; Martin C. J. Maiden; Steven C. Gilbert; Douglas Clark; William G. Wade; David Beighton
Streptococcus oralis is a member of the normal human oral microbiota, capable of opportunistic pathogenicity; like related oral streptococci, it exhibits appreciable phenotypic and genetic variation. A multilocus sequence typing (MLST) scheme for S. oralis was developed and the resultant data analysed to examine the population structure of the species. Analysis of 113 isolates, confirmed as belonging to the S.
Widespread Distribution of a Tet W Determinant among Tetracycline-Resistant Isolates of the Animal Pathogen Arcanobacterium pyogenes
Stephen J. Billington; J. Glenn Songer; B. Helen Jost
Tetracycline resistance is common among isolates of the animal commensal and opportunistic pathogen Arcanobacterium pyogenes. The tetracycline resistance determinant cloned from two bovine isolates of A. pyogenes was highly similar at the DNA level (92% identity) to the tet(W) gene, encoding a ribosomal protection tetracycline resistance protein, from the rumen bacterium Butyrivibrio fibrisolvens. The tet(W) gene was found in all
A Gray-purple Mass on the Floor of the Mouth: Gigantic Mucogingival Pyogenic Granuloma in a Teenage Patient
Brunet-LLobet, Lluís; Miranda-Rius, Jaume; Lahor-Soler, Eduard; Mrina, Ombeni; Nadal, Alfons
Pyogenic granuloma is defined as a benign neoplasm of vascular phenotype. This case describes the clinical and histopathological features of a gigantic mucogingival pyogenic granuloma, in a 14-year-old healthy black boy. This exophytic gray-purple mass, related to a toothpick injury, had more than twelve-month evolution on the anterior mandible involving lingual area besides to the floor of the mouth pressing the right salivary duct. Conservative excision was performed, followed by uncomplicated healing with no recurrence in two years. The histopathological examination reported a pyogenic granuloma (lobular capillary haemangioma). The authors provide a discussion of the presurgical differential diagnosis of the lesion. This case report presents an extremely uncommon location of a gigantic pyogenic granuloma, involving mucogingival complex and affecting the salivary outflow. This clinical manuscript may shed light on the controversies about possible mechanisms inducing oral pyogenic granuloma. PMID:24987485
Establishment of a Streptococcus pneumoniae nasopharyngeal colonization model in adult mice
Hong-Yin Wu; Anni Virolainen; Bonnie Mathews; Janice King; Michael W Russell; David E Briles
Human nasopharyngeal carriage ofStreptococcus pneumoniaeconstitutes the major natural reservoir of pneumococci and is thought to be the prelude to virtually all pneumococcal disease. If carriage could be greatly reduced, pneumococcal transmission and disease could be largely eliminated. To facilitate the studies of mechanisms important in carriage and to identify immunogens that can elicit protection against carriage, we characterized an adult
Replacing and Additive Horizontal Gene Transfer in Streptococcus
Choi, Sang Chul; Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Stanhope, Michael J.; Siepel, Adam
The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria is now well documented, but few studies have differentiated between evolutionary events that predominantly cause genes in one lineage to be replaced by homologs from another lineage ("replacing HGT") and events that result in the addition of substantial new genomic material ("additive HGT"). Here in, we make use of the distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide study of the important human pathogen Streptococcus pyogenes (SPY) and its close relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae subspecies dysgalactiae (SDD). Using recently developed statistical models and computational methods, we find evidence for abundant gene flow of both kinds within each of the SPY and SDE clades and of reduced levels of exchange between SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry in SPY–SDE gene flow, favoring the SPY-to-SDE direction. This finding is of particular interest in light of the recent increase in virulence of pathogenic SDE. We find much stronger evidence for SPY–SDE gene flow among replacing than among additive transfers, suggesting a primary influence from homologous recombination between co-occurring SPY and SDE cells in human hosts. Putative virulence genes are correlated with transfer events, but this correlation is found to be driven by additive, not replacing, HGTs. The genes affected by additive HGTs are enriched for functions having to do with transposition, recombination, and DNA integration, consistent with previous findings, whereas replacing HGTs seen to influence a more diverse set of genes. Additive transfers are also found to be associated with evidence of positive selection. These findings shed new light on the manner in which HGT has shaped pathogenic bacterial genomes. PMID:22617954
Mixed pyogenic and tuberculous liver abscess: clinical suspicion is what matters
Singh, Rajnish; Kumar, Naveen; Sundriyal, Deepak; Trisal, Deepshikha
Tuberculosis (TB) is a rare cause of liver abscess, even in country like India where it is a very common infection. Moreover, tubercular liver abscess (TLA) is the most unusual pattern of hepatic tuberculosis. We report an unusual case of liver abscess in an immune-competent patient presenting only with weight loss. On investigation, initially it appeared pyogenic, but later turn out to be a mixed infection with tuberculosis. He responded well to antibiotic and antitubercular drugs. A mixed pyogenic and TLA is very uncommon. We conclude that, tuberculosis should be suspected in liver abscess, especially in the absence of typical features and failure to respond to antibiotics. PMID:23814224
Understanding the bacterial polysaccharide antigenicity of Streptococcus agalactiae versus Streptococcus pneumoniae
Renuka Kadirvelraj; Jorge Gonzalez-Outeirińo; B. Lachele Foley; Meredith L. Beckham; Harold J. Jennings; Simon Foote; Michael G. Ford; Robert J. Woods
Bacterial surface capsular polysaccharides (CPS) that are similar in carbohydrate sequence may differ markedly in immunogenicity and antigenicity. The structural origin of these phenomena is poorly understood. Such a case is presented by the Gram-positive bacteria Streptococcus agalactiae (Group B Streptococcus; GBS) type III (GBSIII) and Streptococcus pneumoniae (Pn) type 14 (Pn14), which share closely related CPS sequences. Nevertheless, antibodies
Subcutaneous Immunization with Inactivated Bacterial Components and Purified Protein of Escherichia coli, Fusobacterium necrophorum and Trueperella pyogenes Prevents Puerperal Metritis in Holstein Dairy Cows
Machado, Vinícius Silva; Bicalho, Marcela Luccas de Souza; Meira Junior, Enoch Brandăo de Souza; Rossi, Rodolfo; Ribeiro, Bruno Leonardo; Lima, Svetlana; Santos, Thiago; Kussler, Arieli; Foditsch, Carla; Ganda, Erika Korzune; Oikonomou, Georgios; Cheong, Soon Hon; Gilbert, Robert Owen; Bicalho, Rodrigo Carvalho
In this study we evaluate the efficacy of five vaccine formulations containing different combinations of proteins (FimH; leukotoxin, LKT; and pyolysin, PLO) and/or inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes) in preventing postpartum uterine diseases. Inactivated whole cells were produced using two genetically distinct strains of each bacterial species (E. coli, F. necrophorum, and T. pyogenes). FimH and PLO subunits were produced using recombinant protein expression, and LKT was recovered from culturing a wild F. necrophorum strain. Three subcutaneous vaccines were formulated: Vaccine 1 was composed of inactivated bacterial whole cells and proteins; Vaccine 2 was composed of proteins only; and Vaccine 3 was composed of inactivated bacterial whole cells only. Two intravaginal vaccines were formulated: Vaccine 4 was composed of inactivated bacterial whole cells and proteins; and Vaccine 5 was composed of PLO and LKT. To evaluate vaccine efficacy, a randomized clinical trial was conducted at a commercial dairy farm; 371 spring heifers were allocated randomly into one of six different treatments groups: control, Vaccine 1, Vaccine 2, Vaccine 3, Vaccine 4 and Vaccine 5. Late pregnant heifers assigned to one of the vaccine groups were each vaccinated twice: at 230 and 260 days of pregnancy. When vaccines were evaluated grouped as subcutaneous and intravaginal, the subcutaneous ones were found to significantly reduce the incidence of puerperal metritis. Additionally, subcutaneous vaccination significantly reduced rectal temperature at 6±1 days in milk. Reproduction was improved for cows that received subcutaneous vaccines. In general, vaccination induced a significant increase in serum IgG titers against all antigens, with subcutaneous vaccination again being more effective. In conclusion, subcutaneous vaccination with inactivated bacterial components and/or protein subunits of E. coli, F. necrophorum and T. pyogenes can prevent puerperal metritis during the first lactation of dairy cows, leading to improved reproduction. PMID:24638139
Segmental cholangiectasia clinically worrisome for cholangiocarcinoma: comparison with recurrent pyogenic cholangitis.
Zhao, Lei; Hosseini, Mojgan; Wilcox, Rebecca; Liu, Qiang; Crook, Terri; Taxy, Jerome B; Ferrell, Linda; Hart, John
The aim of this study was to review the clinical, radiographic, and pathologic features of cases of benign segmental cholangiectasia in non-Asian US patients with clinical concern for cholangiocarcinoma and compare these features with cases of recurrent pyogenic cholangitis (RPC) in Asian patients. A total of 10 non-Asian US patients with benign segmental cholangiectasia were included in this study. Nine of them underwent partial hepatic resection due to cholangiographic findings of segmental cholangiectasia with mural thickening and/or proximal biliary stricture. One was found to have markedly dilated and thickened intrahepatic bile ducts at the time of autopsy. Clinical and radiographic findings were reviewed. Elastin stains and immunostains for immunoglobulin G4, cluster of differentiation (CD1a), and Langerin were performed. Six comparison cases of RPC in Asian US patients were also examined. Histologic examination of resection specimens revealed markedly dilated large intrahepatic bile ducts with variable degrees of mural fibrosis, periductal gland hyperplasia, inflammation, and liver parenchymal atrophy. These changes were not associated with a ductular reaction. There was no evidence of biliary dysplasia or biliary cirrhosis in any cases. No gross or microscopic feature definitively separated the Asian from non-Asian patients. The etiology of this disorder in non-Asian US patients is unclear. It does not appear to represent a localized variant of Caroli disease or primary sclerosing cholangitis. The high degree of similarity shared by these cases and classic RPC suggests a common pathogenic mechanism, although the pathologic features tend to be less well developed in the cases from the non-Asian US patients. PMID:25600951
Case Report: Group B Streptococcus meningitis in an adolescent
Vittorino, Roselle; Hui-Yuen, Joyce; Ratner, Adam J.; Starr, Amy; McCann, Teresa
Streptococcus agalactiae (group B Streptococcus, GBS) usually colonizes the gastrointestinal and lower genital tracts of asymptomatic hosts, yet the incidence of invasive disease is on the rise . We describe a case of an 18 year old woman, recently diagnosed with lupus, who reported a spontaneous abortion six weeks prior to her hospitalization. She presented with fever, altered mental status, and meningeal signs, paired with a positive blood culture for GBS. Magnetic resonance imaging of her brain demonstrated an extra-axial fluid collection, and she was diagnosed with meningitis. She received prolonged intravenous antibiotic therapy and aggressive treatment for lupus, leading to clinical recovery. This case illustrates the importance of recognizing GBS as a potential pathogen in all patients presenting with CNS infection . PMID:25339988
Mechanisms of genome evolution of Streptococcus.
Andam, Cheryl P; Hanage, William P
The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci. PMID:25461843
Nationwide surveillance of 6 otorhinolaryngological infectious diseases and antimicrobial susceptibility pattern in the isolated pathogens in Japan.
Suzuki, Kenji; Kurono, Yuichi; Ikeda, Katsuhisa; Watanabe, Akira; Iwamoto, Aikichi; Totsuka, Kyoichi; Kaku, Mitsuo; Iwata, Satoshi; Kadota, Jun-Ichi; Hanaki, Hideaki
The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee has conducted a nationwide surveillance on antimicrobial susceptibility patterns and rates of isolation in 6 otolaryngological diseases. The surveillance program was conducted in the otorhinolaryngological departments of 29 universities, and their 26 affiliated hospitals. Patients suffering from acute otitis media, chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess between January 2011 and June 2012 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the drug susceptibility of detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae, Moraxella Catarrhalis, and Pseudomonas aeruginosa), and three anaerobic bacteria (Peptostreptococcus spp., Prevotella spp., and Fusobacterium spp.). Bacterial susceptibility to 39 antimicrobial drugs was investigated. We compared bacterial isolation ratio of each disease in this surveillance from those of past 4 times surveillance which we performed formerly, and we also compared percentage of main drug resistant strains from those of past 4 times surveillance. The age composition between this time and former surveillances was not statistically significant by student-t test. We were unable to completely resolve the rise in resistant bacteria, such as methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, penicillin-intermediate resistant S. pneumoniae, beta-lactamase non-producing ampicillin-resistant H. influenzae, beta-lactamase producing ampicillin-resistant H. influenzae, and beta-lactamase producing amoxicillin clavulanic acid-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial drugs in order to avoid the spread of these bacteria. PMID:26004175
Multiple Pyogenic Granulomas After Burns: Response to Conservative Treatment in Five Children.
Zhao, Hongliang; Zhao, Huanjun; Zhang, Cuiping; Fu, Xiaobing
We describe five children with multiple pyogenic granulomas after burns that were healed effectively using conservative treatment consisting of 1% povidone-iodine, silver nanoparticle dressing, and antibiotics. No relapse of the lesions was observed from 6 months to 2 years later. PMID:25895011
Anterior instrumentation for the treatment of pyogenic vertebral osteomyelitis of thoracic and lumbar spine
Chen, Wei-Hua; Jiang, Lei-Sheng
Anterior radical debridement and bone grafting is popular in the treatment of pyogenic infection of the spine, but there remains great concern of placing instrumentation in the presence of infection because of the potentiality of infection recurrence after surgery. The objective of this study was to prospectively evaluate the efficacy and safety of anterior instrumentation in patients who underwent simultaneous anterior debridement and autogenous bone grafting for the treatment of pyogenic vertebral osteomyelitis. The series consisted of 22 consecutive patients who were treated with anterior debridement, interbody fusion with autogenous bone grafting and anterior instrumentation for pyogenic vertebral osteomyelitis of thoracic and lumbar spine. The patients were prospectively followed up for a minimum of 3 years (average 46.1 months; range 36–74 months). Data were obtained for assessing clinically the neurological function and pain and radiologically the spinal alignment and fusion progress as well as recurrence of the infection. All the patients experienced complete or significant relief of back pain with rapid improvement of neurological function. Kyphosis was improved with an average correction rate of 93.1% (range 84–100%). Solid fusion and healing of the infection was achieved in all the patients without any evidence of recurrent or residual infection. The study shows that combined with perioperative antibiotic regimen, anterior instrumentation is effective and safe in the treatment of pyogenic vertebral osteomyelitis of thoracic and lumbar spine directly following radical debridement and autogenous bone grafting. PMID:18575900
Phacomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome and pyogenic granuloma.
Hagiwara, K; Uezato, H; Nonaka, S
A case of phacomatosis pigmentovascularis (PPV) in a 6-year-old girl with Sturge-Weber syndrome, pyogenic granuloma, and other complications is described. It is relatively rare that a complete form of Sturge-Weber syndrome was associated with PPV. A review of the literature on PPV, focusing on total number of reported cases and etiological speculations, is presented. To our knowledge, a total of 118 cases of PPV, including the present one, have been reported to date. Regardless of many speculations, the true etiology remains unknown. The average "density" of mast cells (MCs) per mm2 appearing in the central region of the pyogenic granuloma was calculated to be 86.3/mm2 and that in the adjacent nevus flammeus was 37.9/mm2. The "density" of mast cells in pyogenic granuloma separately calculated from ten other cases was 105.5 +/- 28.6/mm2 (mean +/- SD), compared with that in normal skin, 6.85 +/- 4.9/mm2 (n = 20). There was a significant difference between the two, indicating that MCs are closely associated with angiogenesis in pyogenic granuloma. PMID:9863285
Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behçet's syndrome.
Lehner, T; Lavery, E; Smith, R; van der Zee, R; Mizushima, Y; Shinnick, T
The etiology of Behcet's syndrome (BS) is unknown, but a number of streptococcal species have been implicated. A hypothesis was postulated that a shared antigen, such as a stress protein, might account for some of these findings. Indeed, a rabbit antiserum against a 65-kDa heat shock protein of Mycobacterium tuberculosis revealed a corresponding 65-kDa band with all six Streptococcus sanguis strains examined and S. pyogenes but not with S. salivarius. By applying a panel of nine monoclonal antibodies to the mycobacterial 65-kDa heat shock protein, an approximately 65-kDa antigen was identified in the uncommon serotypes of S. sanguis ST3 and H.83 and one with a different Mr was identified in KTH-1 and S. pyogenes. Monoclonal antibodies Y1.2, C1.1, II H9, and ML30, which reacted with these streptococci, recognize residues 11 to 27, 88 to 123, 107 to 122, and 276 to 297 of the 65-kDa heat shock protein, respectively, suggesting that these residues are conserved among some uncommon serotypes of S. sanguis and S. pyogenes. Immunoblot analyses of sera from patients with BS for immunoglobulin A (IgA) and IgG antibodies revealed bands of 65 to 70 kDa with the mycobacterial heat shock protein, S. sanguis strains, and S. pyogenes, although these reactivities were also found to a lesser extent in controls. A 65- to 70-kDa band was found more frequently with S. sanguis KTH-2 or KTH-3 and IgA in serum from patients with BS than with serum from controls (P less than 0.02). Antibodies in serum were then studied by a radioimmunoassay, and in patients with BS this revealed significantly raised IgA antibodies to the recombinant 65-kDa mycobacterial heat shock protein and to soluble protein extracts of S. sanguis ST3, KTH-1, KTH-2, and KTH-3. Whereas significant anti-65-kDa heat shock protein and anti-S. sanguis ST3 antibodies were also found in sera from patients with rheumatoid arthritis and recurrent oral ulcers, the anti-S. sanguis KTH-1, KTH-2, and KTH-3 antibodies were confined to BS. The results are consistent with the hypothesis that some of the streptococcal antigens are associated with heat shock or stress proteins, which will need to be formally established by isolating heat shock proteins from streptococci. Images PMID:2004821
Localised mitogenic activity in horses following infection with Streptococcus equi.
McLean, R; Rash, N L; Robinson, C; Waller, A S; Paillot, R
Streptococcus equi subspecies equi (S.?equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S.?equi. The aim of this study was to determine the sites of sAg production during infection and therefore improve our understanding of their role. Abscess material, chondroids and serum collected from Equidae with signs of strangles were tested in mitogenic assays. Mitogenic sAg activity was only detected in abscess material and chondroids. Our data support the localised in vivo activity of sAg during both acute and carrier phases of S.?equi infection. PMID:25841794
Generic determinants of Streptococcus colonization and infection.
Nobbs, Angela H; Jenkinson, Howard F; Everett, Dean B
Bacteria within the genus Streptococcus have evolved to become exquisitely adapted to the colonization of humans and other animals. These bacteria predominantly live in harmony with their hosts, but all have capacity to cause disease should prevailing conditions allow. Streptococci express a myriad of colonization and virulence attributes that promote their survival at a variety of ecological sites. Many of these factors are surface-expressed adhesins that exhibit conservation at structural or functional levels across the genus. This reflects the importance of adherence interactions with a multitude of host substrata, such as epithelia or extracellular matrix components, to streptococcal survival. Other important factors are more restricted in their distribution, often conferring pathogenic capabilities associated with immune evasion or host tissue destruction. Evidence suggests that dissemination of these streptococcal attributes has frequently been driven by the movement of genetic material via lateral gene transfer, reflecting ecological pressures. Such recombination events have simultaneously facilitated extensive diversification, resulting in distinct tropisms at the species- or strain- level. These generic determinants offer significant potential as targets for combating streptococcal disease. However, this will depend upon better understanding of their mechanistic basis, and refined mapping of their distribution by epidemiological and metagenomic studies. PMID:25246075
Human Streptococcus agalactiae strains in aquatic mammals and fish
Background In humans, Streptococcus agalactiae or group B streptococcus (GBS) is a frequent coloniser of the rectovaginal tract, a major cause of neonatal infectious disease and an emerging cause of disease in non-pregnant adults. In addition, Streptococcus agalactiae causes invasive disease in fish, compromising food security and posing a zoonotic hazard. We studied the molecular epidemiology of S. agalactiae in fish and other aquatic species to assess potential for pathogen transmission between aquatic species and humans. Methods Isolates from fish (n = 26), seals (n = 6), a dolphin and a frog were characterized by pulsed-field gel electrophoresis, multilocus sequence typing and standardized 3-set genotyping, i.e. molecular serotyping and profiling of surface protein genes and mobile genetic elements. Results Four subpopulations of S. agalactiae were identified among aquatic isolates. Sequence type (ST) 283 serotype III-4 and its novel single locus variant ST491 were detected in fish from Southeast Asia and shared a 3-set genotype identical to that of an emerging ST283 clone associated with invasive disease of adult humans in Asia. The human pathogenic strain ST7 serotype Ia was also detected in fish from Asia. ST23 serotype Ia, a subpopulation that is normally associated with human carriage, was found in all grey seals, suggesting that human effluent may contribute to microbial pollution of surface water and exposure of sea mammals to human pathogens. The final subpopulation consisted of non-haemolytic ST260 and ST261 serotype Ib isolates, which belong to a fish-associated clonal complex that has never been reported from humans. Conclusions The apparent association of the four subpopulations of S. agalactiae with specific groups of host species suggests that some strains of aquatic S. agalactiae may present a zoonotic or anthroponotic hazard. Furthermore, it provides a rational framework for exploration of pathogenesis and host-associated genome content of S. agalactiae strains. PMID:23419028
Streptococcus mutans out-competes Streptococcus gordonii in vivo.
Tanzer, J M; Thompson, A; Sharma, K; Vickerman, M M; Haase, E M; Scannapieco, F A
Streptococcus gordonii and Streptococcus mutans avidly colonize teeth. S. gordonii glucosyltransferase (GtfG) and amylase-binding proteins (AbpA/AbpB), and S. mutans glucosyltransferase (GtfB), affect their respective oral colonization abilities. We investigated their interrelationships and caries association in a rat model of human caries, examining the sequence of colonization and non- vs. high-sucrose diets, the latter being associated with aggressive decay in humans and rats. Virulence-characterized wild-types of both species and well-defined mutants of S. gordonii with interrupted abpA and gtfG genes were studied. While both S. gordonii and S. mutans were abundant colonizers of rat's teeth in the presence of either diet, if inoculated singly, S. mutans always out-competed S. gordonii on the teeth, independent of diet, strain of S. mutans, simultaneous or sequential inoculation, or presence/absence of mutations of S. gordonii's abpA and gtfG genes known to negatively or positively affect its colonization and to interact in vitro with S. mutans GtfB. S. mutans out-competed S. gordonii in in vivo plaque biofilm. Caries induction reflected S. mutans or S. gordonii colonization abundance: the former highly cariogenic, the latter not. S. gordonii does not appear to be a good candidate for replacement therapy. These results are consistent with human data. PMID:22431892
Streptococcus mutans Out-competes Streptococcus gordonii in vivo
Tanzer, J. M.; Thompson, A.; Sharma, K.; Vickerman, M.M.; Haase, E.M.; Scannapieco, F.A.
Streptococcus gordonii and Streptococcus mutans avidly colonize teeth. S. gordonii glucosyltransferase (GtfG) and amylase-binding proteins (AbpA/AbpB), and S. mutans glucosyltransferase (GtfB), affect their respective oral colonization abilities. We investigated their interrelationships and caries association in a rat model of human caries, examining the sequence of colonization and non- vs. high-sucrose diets, the latter being associated with aggressive decay in humans and rats. Virulence-characterized wild-types of both species and well-defined mutants of S. gordonii with interrupted abpA and gtfG genes were studied. While both S. gordonii and S. mutans were abundant colonizers of rat's teeth in the presence of either diet, if inoculated singly, S. mutans always out-competed S. gordonii on the teeth, independent of diet, strain of S. mutans, simultaneous or sequential inoculation, or presence/absence of mutations of S. gordonii's abpA and gtfG genes known to negatively or positively affect its colonization and to interact in vitro with S. mutans GtfB. S. mutans out-competed S. gordonii in in vivo plaque biofilm. Caries induction reflected S. mutans or S. gordonii colonization abundance: the former highly cariogenic, the latter not. S. gordonii does not appear to be a good candidate for replacement therapy. These results are consistent with human data. PMID:22431892
Streptococcus milleri in the appendix.
Poole, P M; Wilson, G
The appendix was investigated as a possible habitat of Streptococcus milleri. Both normal and inflamed appendices were examined and the isolation rates compared. S. milleri was present in a quarter of the normal appendices and more than half of those associated with apendicitis--a difference that was statistically highly significant. The isolation rates throughout were indepencent of age. There was a pronounced connection between the presence of S. milleri in the appendix and the purulent manifestations of appendicitis. S. milleri was isolated from other abdominal sites associated with appendicitis. The frequency of isolation was increased by culture in an enrichment broth containing nalidixic acid and sulphadimidine. PMID:591633
Streptococcus milleri in the appendix.
Poole, P M; Wilson, G
The appendix was investigated as a possible habitat of Streptococcus milleri. Both normal and inflamed appendices were examined and the isolation rates compared. S. milleri was present in a quarter of the normal appendices and more than half of those associated with apendicitis--a difference that was statistically highly significant. The isolation rates throughout were indepencent of age. There was a pronounced connection between the presence of S. milleri in the appendix and the purulent manifestations of appendicitis. S. milleri was isolated from other abdominal sites associated with appendicitis. The frequency of isolation was increased by culture in an enrichment broth containing nalidixic acid and sulphadimidine. PMID:591633
Arrangement and number of clustered regularly interspaced short palindromic repeat spacers are associated with erythromycin susceptibility in emm12, emm75 and emm92 of group A streptococcus.
Zheng, P-X; Chiang-Ni, C; Wang, S-Y; Tsai, P-J; Kuo, C-F; Chuang, W-J; Lin, Y-S; Liu, C-C; Wu, J-J
Clustered regularly interspaced short palindromic repeats (CRISPR) are composed of numerous repeat-spacer units and are considered a prokaryotic defence system against foreign nucleic acids. Since antibiotic-resistant genes are frequently encoded in foreign nucleic acids, the aim of this study was to test whether erythromycin susceptibility in group A streptococcus (Streptococcus pyogenes) is associated with characteristics of CRISPR elements. Erythromycin susceptibility of 330 isolates collected between 1997 and 2003 was analysed. Among 29 emm types, emm12, emm75 and emm92 showed significant changes in erythromycin-resistance rates. By sequencing the spacers from two CRISPR loci, spacer contents in emm12, emm75 and emm92 strains were associated with erythromycin susceptibility. Strains with fewer spacers were more resistant to erythromycin. Moreover, in emm4 strains, which showed no significant change in their annual erythromycin-resistance rate, CRISPR type and number of spacers were not correlated with erythromycin susceptibility. These results highlight a novel association between CRISPR spacer content and erythromycin susceptibility in group A streptococcus. PMID:24118239
Paclitaxel-associated subungual pyogenic granuloma: report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail.
Paul, Laura J; Cohen, Philip R
Subungual and periungual pyogenic granuloma occur in association with certain systemic medications. Paclitaxel is an antitumor drug of the taxane family used in the management of breast cancer. Taxanes have many associated nail changes that may occur in patients receiving either docetaxel or paclitaxel for systemic chemotherapy. The nail changes in a 68-year-old woman with metastatic breast cancer who presented for nail changes after receiving 12 cycles of weekly paclitaxel are described herein: nail plate red-brown discoloration, onycholysis with leukonychia, proximal subungual hemorrhage, and subungual pyogenic granuloma. The literature on systemic medications associated with the development of subungual and periungual pyogenic granulomas is reviewed; drugs associated with the development of pyogenic granuloma at the locations include antineoplastics, antiretrovirals, epidermal growth factor receptor inhibitors, immunosuppressants and retinoids. In conclusion, subungual pyogenic granuloma can occur not only in patients receiving docetaxel, but also in patients treated with paclitaxel. And, paclitaxel should be included in the list of drugs associated with the occurrence of subungual pyogenic granuloma. PMID:22270214
Intracellular ?-Amylase of Streptococcus mutans
Simpson, Christine L.; Russell, Roy R. B.
Sequencing upstream of the Streptococcus mutans gene for a CcpA gene homolog, regM, revealed an open reading frame, named amy, with homology to genes encoding ?-amylases. The deduced amino acid sequence showed a strong similarity (60% amino acid identity) to the intracellular ?-amylase of Streptococcus bovis and, in common with this enzyme, lacked a signal sequence. Amylase activity was found only in S. mutans cell extracts, with no activity detected in culture supernatants. Inactivation of amy by insertion of an antibiotic resistance marker confirmed that S. mutans has a single ?-amylase activity. The amylase activity was induced by maltose but not by starch, and no acid was produced from starch. S. mutans can, however, transport limit dextrins and maltooligosaccharides generated by salivary amylase, but inactivation of amy did not affect growth on these substrates or acid production. The amylase digested the glycogen-like intracellular polysaccharide (IPS) purified from S. mutans, but the amy mutant was able to digest and produce acid from IPS; thus, amylase does not appear to be essential for IPS breakdown. However, when grown on excess maltose, the amy mutant produced nearly threefold the amount of IPS produced by the parent strain. The role of Amy has not been established, but Amy appears to be important in the accumulation of IPS in S. mutans grown on maltose. PMID:9721315
The Isolation and Cultural Characteristics of Streptococcus pluton and further Observations on Bacterium eurydice
L. Bailey
SUMMARY: An account is given of the development of a reliable method for the isolation of Streptococcus pluton (Bacillus pluton White), an organism associated with European foul-brood disease of the larval honeybee. S. pluton, isolated as an anaerobe, may be trained to grow as an aerobe in rod form. Its principal anaerobic growth requirements are a low molar ratio of
Identification and Epidemiology of Streptococcus iniae and S. agalactiae in tilapias Oreochromis spp.
Technology Transfer Automated Retrieval System (TEKTRAN)
Despite being known mainly as mammalian disease agents, Streptococcus iniae and S. agalactiae have become recognized as emerging pathogens of wild and cultured fish. The worldwide economic impact of S. iniae and S. agalactiae to the aquaculture industry is estimated in hundreds of millions annually...
[Acute epiglottitis due to group A ?-hemolytic streptococcus in a child].
Mazenq, J; Retornaz, K; Vialet, R; Dubus, J-C
Acute epiglottitis has become an exceptional observation in pediatrics. The introduction of Haemophilus influenzae type B vaccine changed the morbidity, mortality, and microbiology of this disease. We report the case of an 11-month-old infant with acute epiglottitis due to group A ?-hemolytic streptococcus. PMID:25282454
Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from 1993 to 2011
Kaplan, Sheldon L.; Lamberth, Linda B.; Barson, William J.; Romero, José R.; Lin, Philana Ling; Bradley, John S.; Givner, Laurence B.; Tan, Tina Q.; Hoffman, Jill A.; Mason, Edward O.
Among 594 Streptococcus pneumoniae serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction. PMID:23390277
High Prevalence of Antimicrobial Resistance among Clinical Streptococcus pneumoniae Isolates in Asia (an ANSORP Study)
Jae-Hoon Song; Sook-In Jung; Kwan Soo Ko; Na Young Kim; Jun Seong Son; Hyun-Ha Chang; Hyun Kyun Ki; Won Sup Oh; Ji Yoeun Suh; Kyong Ran Peck; Nam Yong Lee; Yonghong Yang; Quan Lu; Anan Chongthaleong; Cheng-Hsun Chiu; M. K. Lalitha; Jennifer Perera; Ti Teow Yee; Gamini Kumarasinghe; Farida Jamal; Adeeba Kamarulzaman; N. Parasakthi; P. H. Van; C. Carlos; T. So; T. K. Ng; A. Shibl
A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate,
Transcriptional Regulation in the Streptococcus pneumoniae rlrA Pathogenicity Islet by RlrA
David L. Hava; Carolyn J. Hemsley; Andrew Camilli
The proper temporal expression of virulence genes during infection is crucial to the infectious life cycle of microbial pathogens, particularly in pathogens that encounter a multitude of environments in eukaryotic hosts. Streptococcus pneumoniae normally colonizes the nasopharynges of healthy adults but can cause a range of diseases at a variety of host sites. Transcriptional regulators that are essential for full
Structure-Informed Design of an Enzymatically Inactive Vaccine Component for Group A Streptococcus
Henningham, Anna; Ericsson, Daniel J.; Langer, Karla; Casey, Lachlan W.; Jovcevski, Blagojce; Chhatwal, G. Singh; Aquilina, J. Andrew; Batzloff, Michael R.; Kobe, Bostjan; Walker, Mark J.
ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) causes ~700 million human infections/year, resulting in >500,000 deaths. There is no commercial GAS vaccine available. The GAS surface protein arginine deiminase (ADI) protects mice against a lethal challenge. ADI is an enzyme that converts arginine to citrulline and ammonia. Administration of a GAS vaccine preparation containing wild-type ADI, a protein with inherent enzymatic activity, may present a safety risk. In an approach intended to maximize the vaccine safety of GAS ADI, X-ray crystallography and structural immunogenic epitope mapping were used to inform vaccine design. This study aimed to knock out ADI enzyme activity without disrupting the three-dimensional structure or the recognition of immunogenic epitopes. We determined the crystal structure of ADI at 2.5 Ĺ resolution and used it to select a number of amino acid residues for mutagenesis to alanine (D166, E220, H275, D277, and C401). Each mutant protein displayed abrogated activity, and three of the mutant proteins (those with the D166A, H275A, and D277A mutations) possessed a secondary structure and oligomerization state equivalent to those of the wild type, produced high-titer antisera, and avoided disruption of B-cell epitopes of ADI. In addition, antisera raised against the D166A and D277A mutant proteins bound to the GAS cell surface. The inactivated D166A and D277A mutant ADIs are ideal for inclusion in a GAS vaccine preparation. There is no human ortholog of ADI, and we confirm that despite limited structural similarity in the active-site region to human peptidyl ADI 4 (PAD4), ADI does not functionally mimic PAD4 and antiserum raised against GAS ADI does not recognize human PAD4. PMID:23919999
Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess.
Hsieh, Pei-Fang; Lin, Tzu-Lung; Yang, Feng-Ling; Wu, Meng-Chuan; Pan, Yi-Jiun; Wu, Shih-Hsiung; Wang, Jin-Town
Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K(1) (-) O(1)) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain. PMID:22427976
Lipopolysaccharide O1 Antigen Contributes to the Virulence in Klebsiella pneumoniae Causing Pyogenic Liver Abscess
Hsieh, Pei-Fang; Lin, Tzu-Lung; Yang, Feng-Ling; Wu, Meng-Chuan; Pan, Yi-Jiun; Wu, Shih-Hsiung; Wang, Jin-Town
Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K1? O1) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain. PMID:22427976
Quorum sensing in group A Streptococcus
Jimenez, Juan Cristobal; Federle, Michael J.
Quorum sensing (QS) is a widespread phenomenon in the microbial world that has important implications in the coordination of population-wide responses in several bacterial pathogens. In Group A Streptococcus (GAS), many questions surrounding QS systems remain to be solved pertaining to their function and their contribution to the GAS lifestyle in the host. The QS systems of GAS described to date can be categorized into four groups: regulator gene of glucosyltransferase (Rgg), Sil, lantibiotic systems, and LuxS/AI-2. The Rgg family of proteins, a conserved group of transcription factors that modify their activity in response to signaling peptides, has been shown to regulate genes involved in virulence, biofilm formation and competence. The sil locus, whose expression is regulated by the activity of signaling peptides and a putative two-component system (TCS), has been implicated on regulating genes involved with invasive disease in GAS isolates. Lantibiotic regulatory systems are involved in the production of bacteriocins and their autoregulation, and some of these genes have been shown to target both bacterial organisms as well as processes of survival inside the infected host. Finally AI-2 (dihydroxy pentanedione, DPD), synthesized by the LuxS enzyme in several bacteria including GAS, has been proposed to be a universal bacterial communication molecule. In this review we discuss the mechanisms of these four systems, the putative functions of their targets, and pose critical questions for future studies. PMID:25309879
Identification of Trueperella pyogenes Isolated from Bovine Mastitis by Fourier Transform Infrared Spectroscopy
Nagib, Samy; Rau, Jörg; Sammra, Osama; Lämmler, Christoph; Schlez, Karen; Zschöck, Michael; Prenger-Berninghoff, Ellen; Klein, Guenter; Abdulmawjood, Amir
The present study was designed to investigate the potential of Fourier transform infrared (FT-IR) spectroscopy to identify Trueperella (T.) pyogenes isolated from bovine clinical mastitis. FT-IR spectroscopy was applied to 57 isolates obtained from 55 cows in a period from 2009 to 2012. Prior to FT-IR spectroscopy these isolates were identified by phenotypic and genotypic properties, also including the determination of seven potential virulence factor encoding genes. The FT-IR analysis revealed a reliable identification of all 57 isolates as T. pyogenes and a clear separation of this species from the other species of genus Trueperella and from species of genus Arcanobacterium and Actinomyces. The results showed that all 57 isolates were assigned to the correct species indicating that FT-IR spectroscopy could also be efficiently used for identification of this bacterial pathogen. PMID:25133407
Pyogenic granuloma, an unusual presentation of peripubertal vaginal bleeding. Case report and review of the literature.
Barasoain-Millán, Alberto; Rodriguez-Contreras, Francisco Javier; Guerrero-Fernandez, Julio; Merino, Maria Beato; Gonzalez-Casado, Isabel
Pyogenic granuloma, also named lobular capillary hemangioma, is a common proliferative vascular lesion known as a benign condition despite its rapid growth. It may appear in any cutaneous or mucosal surface but is usually restricted to the oral cavity. It is characterized by a friable mulberry-like lesion that can be sessile or pedunculated. Bleeding is usually its first clinical manifestation. Locations on respiratory, digestive and genital tracts are uncommon and sporadic. We describe the occurrence of an intravaginal pyogenic granuloma in a peripubertal girl with recurrent vaginal bleeding. This is the first reported case of a genital tract lobular capillary hemangioma in pediatric age to our knowledge. Therefore, we suggest this entity in the differential diagnosis of an unclear peripubertal vaginal bleeding. PMID:25324441
Inhibition of Streptococcus mutans biofilm formation by Streptococcus salivarius FruA.
Ogawa, Ayako; Furukawa, Soichi; Fujita, Shuhei; Mitobe, Jiro; Kawarai, Taketo; Narisawa, Naoki; Sekizuka, Tsuyoshi; Kuroda, Makoto; Ochiai, Kuniyasu; Ogihara, Hirokazu; Kosono, Saori; Yoneda, Saori; Watanabe, Haruo; Morinaga, Yasushi; Uematsu, Hiroshi; Senpuku, Hidenobu
The oral microbial flora consists of many beneficial species of bacteria that are associated with a healthy condition and control the progression of oral disease. Cooperative interactions between oral streptococci and the pathogens play important roles in the development of dental biofilms in the oral cavity. To determine the roles of oral streptococci in multispecies biofilm development and the effects of the streptococci in biofilm formation, the active substances inhibiting Streptococcus mutans biofilm formation were purified from Streptococcus salivarius ATCC 9759 and HT9R culture supernatants using ion exchange and gel filtration chromatography. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry analysis was performed, and the results were compared to databases. The S. salivarius HT9R genome sequence was determined and used to indentify candidate proteins for inhibition. The candidates inhibiting biofilms were identified as S. salivarius fructosyltransferase (FTF) and exo-beta-d-fructosidase (FruA). The activity of the inhibitors was elevated in the presence of sucrose, and the inhibitory effects were dependent on the sucrose concentration in the biofilm formation assay medium. Purified and commercial FruA from Aspergillus niger (31.6% identity and 59.6% similarity to the amino acid sequence of FruA from S. salivarius HT9R) completely inhibited S. mutans GS-5 biofilm formation on saliva-coated polystyrene and hydroxyapatite surfaces. Inhibition was induced by decreasing polysaccharide production, which is dependent on sucrose digestion rather than fructan digestion. The data indicate that S. salivarius produces large quantities of FruA and that FruA alone may play an important role in multispecies microbial interactions for sucrose-dependent biofilm formation in the oral cavity. PMID:21239559
Photodynamic inactivation of Streptococcus mutans and Streptococcus sanguinis biofilms in vitro.
Pereira, Cristiane Aparecida; Costa, Anna Carolina Borges Pereira; Carreira, Claudia Moura; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso
The purpose of this study was to evaluate specific effects of photodynamic inactivation (PDI) using erythrosine (ER) and Rose Bengal (RB) photosensitizers and a blue light-emitting diode (LED) on the viability of Streptococcus mutans and Streptococcus sanguinis biofilms. Biofilms were grown in acrylic disks immersed in broth to production of biofilms, inoculated with microbial suspension (10(6) cells/mL) and incubated for 48 h. After the formation of biofilms, the effects of the photosensitizers ER and RB at a concentration of 5 ?M for 5 min and blue LED (455 ± 20 nm) for 180 s, photosensitizers alone and conjugated were evaluated. Next, the disks were placed in tubes with sterile physiological solution (0.9 % sodium chloride) and sonicated for to disperse the biofilms. Tenfold serial dilutions were carried and aliquots seeded in brain heart infusion agar which were then incubated for 48 h. Then the numbers colony-forming units per milliliter (CFU/mL; log10) were counted and analyzed statistically (ANOVA, Tukey test, P ? 0.05). Significant decreases in the viability of all microorganisms were observed for biofilms exposed to PDI mediated by both photosensitizers. The reductions with RB and ER were, 0.62 and 0.52 log10 CFU mL(-1) for S. mutans biofilms (p=0.001), and 0.95 and 0.88 log10 CFU mL(-1) for S. sanguinis biofilms (p=0.001), respectively. The results showed that biofilms formed in vitro by S. mutans and S. sanguinis, were sensitive to PDI using a blue LED associated with photosensitizers ER or RB, indicating its use in the control of caries and periodontal diseases. PMID:22847685
Atlantoaxial subluxation after pyogenic spondylitis of the atlanto-occipital joint
Kazuhiko Tsunoda; Haku Iizuka; Yasunori Sorimachi; Tsuyoshi Ara; Masahiro Nishinome; Yasuhiko Takechi; Kenji Takagishi
This report presents a case of atlanto-axial subluxation after treatment of pyogenic spondylitis of the atlanto-occipital\\u000a joint. A 60-year-old male had 1-month history of neck pain with fever. Magnetic resonance imaging showed inflammation around\\u000a the odontoid process. Intravenous antibiotic therapy was administrated immediately. After 6 weeks, CRP had returned almost\\u000a to normal. After 4 months, laboratory data was still normal, but the
Minimum inhibitory concentrations of selected antimicrobials against Escherichia coli and Trueperella pyogenes of bovine uterine origin.
de Boer, Melvin; Heuer, Cord; Hussein, Hassan; McDougall, Scott
Minimum inhibitory concentrations (MIC) of 9 antimicrobials for isolates of 2 common bovine intrauterine bacterial pathogens, Escherichia coli (n=209) and Trueperella pyogenes (n=35), were determined using broth microdilution methodology. The isolates were recovered from dairy cows from 7 herds postpartum using the cytobrush technique. The pathogens were initially identified using phenotypic techniques. Additionally, PCR was used to confirm the identity of T. pyogenes isolates and to categorize the E. coli isolates into phylogenetic groups A, B1, B2, and D. Minimum inhibitory concentrations in excess of published cut-points or bimodal distributions of MIC indicated potential antimicrobial resistance to ampicillin, cefuroxime, cephapirin, and oxytetracycline for E. coli, and to oxytetracycline for T. pyogenes. Of the antimicrobials tested, ticarcillin/clavulanic acid, ceftiofur, and enrofloxacin had the lowest MIC for these 2 pathogens. Differences in MIC of some antimicrobials were found between herds, age, breeds, and E. coli phylogenetic groups. Isolation of E. coli with an MIC ?8?g/mL of oxytetracycline at 23d postpartum was associated with a lower probability of pregnancy within 6wk of commencement of breeding compared with those isolates with an MIC <8?g/mL (relative risk=0.66). Minimum inhibitory concentrations for uterine pathogens were determined for isolates from New Zealand dairy cows. However, in the absence of either epidemiological or clinical interpretive criteria, the interpretation of these MIC remains unclear. Further studies are required to define interpretative criteria, including determination of pharmacokinetic and pharmacodynamic profiles for antimicrobials. PMID:25935246
Manganese Affects Streptococcus mutans Virulence Gene Expression
P. Arirachakaran; E. Benjavongkulchai; S. Luengpailin; J. A. Banas
Background\\/Aims: Studies of trace metals in drinking water and tooth enamel have suggested a caries-promoting potential for manganese (Mn). Additionally, Mn has been shown to be essential for the expression of mutans streptococci virulence factors such as the glucan-binding lectin (GBL) of Streptococcus sobrinus. The Streptococcus mutans glucan-binding protein (Gbp) GbpC is the functional analogue of the S. sobrinus GBL.
Technology Transfer Automated Retrieval System (TEKTRAN)
The ability of Streptococcus agalactiae and Streptococcus iniae to attract macrophages of Nile tilapia (Oreochromis niloticus) was investigated. The extracellular products (ECP) from S. agalactiae and S. iniae were tested for macrophage chemotaxis using in vitro blind well chambers. The macrophage...
Functional amyloid formation by Streptococcus mutans
Oli, M. W.; Otoo, H. N.; Crowley, P. J.; Heim, K. P.; Nascimento, M. M.; Ramsook, C. B.; Lipke, P. N.
Dental caries is a common infectious disease associated with acidogenic and aciduric bacteria, including Streptococcus mutans. Organisms that cause cavities form recalcitrant biofilms, generate acids from dietary sugars and tolerate acid end products. It has recently been recognized that micro-organisms can produce functional amyloids that are integral to biofilm development. We now show that the S. mutans cell-surface-localized adhesin P1 (antigen I/II, PAc) is an amyloid-forming protein. This conclusion is based on the defining properties of amyloids, including binding by the amyloidophilic dyes Congo red (CR) and Thioflavin T (ThT), visualization of amyloid fibres by transmission electron microscopy and the green birefringent properties of CR-stained protein aggregates when viewed under cross-polarized light. We provide evidence that amyloid is present in human dental plaque and is produced by both laboratory strains and clinical isolates of S. mutans. We provide further evidence that amyloid formation is not limited to P1, since bacterial colonies without this adhesin demonstrate residual green birefringence. However, S. mutans lacking sortase, the transpeptidase enzyme that mediates the covalent linkage of its substrates to the cell-wall peptidoglycan, including P1 and five other proteins, is not birefringent when stained with CR and does not form biofilms. Biofilm formation is inhibited when S. mutans is cultured in the presence of known inhibitors of amyloid fibrillization, including CR, Thioflavin S and epigallocatechin-3-gallate, which also inhibited ThT uptake by S. mutans extracellular proteins. Taken together, these results indicate that S. mutans is an amyloid-forming organism and suggest that amyloidogenesis contributes to biofilm formation by this oral microbe. PMID:23082034
Urease production by Streptococcus thermophilus.
Zotta, Teresa; Ricciardi, Annamaria; Rossano, Rocco; Parente, Eugenio
In order to identify potential alternative sources of urease for the removal of urea from alcoholic beverages, 205 strains of lactic acid bacteria belonging to 27 different species were screened for urease production. Only Streptococcus thermophilus produced urease. Cell permeabilization with toluene allowed to increase activity significantly. Optimal pH for urease activity in whole and permeabilized cells and of cell free extracts differed slightly, but was in the range 6.0-7.0. Significant activity was retained at pH 3.0 and 8.0, and, for cell free extracts, at pH 4.0 in the presence of ethanol. Urease production was evaluated in fermentations with pH control (5.25-6.5) and without pH control. Very little urease was produced in absence of urea, which at 5g/l slowed growth significantly in fermentations without pH control, but prevented a decrease in pH below 5.1 and resulted in higher final biomass. Optimal pH for growth was between 6.0 and 6.5 but specific urease activity was higher for fermentations at low pH at the beginning of the exponential phase. However, a higher total urease activity was obtained at pH 6.0 and 6.5 because of higher biomass. Potential technological applications of urease production by S. thermophilus are discussed. PMID:17993384
Biofilm formation in Streptococcus pneumoniae
Domenech, Mirian; García, Ernesto; Moscoso, Miriam
Summary Biofilm?grown bacteria are refractory to antimicrobial agents and show an increased capacity to evade the host immune system. In recent years, studies have begun on biofilm formation by Streptococcus pneumoniae, an important human pathogen, using a variety of in vitro model systems. The bacterial cells in these biofilms are held together by an extracellular matrix composed of DNA, proteins and, possibly, polysaccharide(s). Although neither the precise nature of these proteins nor the composition of the putative polysaccharide(s) is clear, it is known that choline?binding proteins are required for successful biofilm formation. Further, many genes appear to be involved, although the role of each appears to vary when biofilms are produced in batch or continuous culture. Prophylactic and therapeutic measures need to be developed to fight S.?pneumoniae biofilm formation. However, much care needs to be taken when choosing strains for such studies because different S.?pneumoniae isolates can show remarkable genomic differences. Multispecies and in vivo biofilm models must also be developed to provide a more complete understanding of biofilm formation and maintenance. PMID:21906265
Diseases of captive marine mammals
D. O. Cordes; P. J. OHara
This paper summarises the diseases observed over a 5-year-period in 29 marine mammals which died in a marine zoological park. Cholangiohepatitis associated with the trematode Campulla palliata was a common finding in dolphins (Delphinus delphis), and septicaemias due to Staphylococcus pyogenes and Erysipelothrix rhusiopathiae were recorded.A New Zealand fur seal (Arctocephalus forsteri) died of salmonellosis due to Salmonella newport, a
Monoclonal Idiotope Vaccine against Streptococcus pneumoniae Infection
NASA Astrophysics Data System (ADS)
McNamara, Mary K.; Ward, Ronald E.; Kohler, Heinz
A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.
Rhinophyma-like hypertrophy of the nose caused by chronic facial pyoderma in a patient with Crohn's disease.
Tsuchiya, Sunao; Ichioka, Shigeru; Tajima, Saori
We present our experience with a 22-year-old man who had Crohn's disease with rhinophyma-like hypertrophy of the nose arising from pyogenic skin disease of the face. The clinical appearance did not precisely match any previously reported skin diseases. PMID:23834302
Complete Genome Sequence of Streptococcus iniae YSFST01-82, Isolated from Olive Flounder in Jeju, South Korea
Rajoo, Sasikumar; Jeon, Wooyoung; Park, Kyungmoon; Yoo, Sungsik; Yoon, Injung; Lee, Hongweon
Streptococcus iniae is associated with morbidity in commercial fish species, especially in olive flounders (Paralichthys olivaceus), and was recently identified as an emerging human pathogen. Here, we report the complete 2.09-Mb genome sequence of S. iniae strain YSFST01-82, isolated from an olive flounder with streptococcosis disease in Jeju, South Korea. PMID:25908134
Persistent occurrence of a single Streptococcus equi subsp. zooepidemicus clone in the pig and monkey population in Indonesia
Siti Isrina; Oktavia Salasia; I Wayan; Teguh Wibawan; Fachriyan H. Pasaribu; Amir Abdulmawjood; Christoph Lämmler
In the present study 41 mucoid growing Streptococcus equi subsp. zooepidemicus strains (37 strains isolated from healthy two from diseased pigs, two strains isolated from healthy monkeys) appeared to be phenotypically and genotypically identical to mucoid growing S. equi subsp. zooepidemicus strains isolated from a previously described outbreak among the pig and monkey population on the island of Bali, Indonesia.
Host and Bacterial Factors Contributing to the Clearance of Colonization by Streptococcus pneumoniae in a Murine Model
A. M. C. van Rossum; E. S. Lysenko; J. N. Weiser
Nasopharyngeal colonization is the first step in the interaction between Streptococcus pneumoniae (the pneumococcus) and its human host. Factors that contribute to clearance of colonization are likely to affect the spread of the pneumococcus and the rate of pneumococcal disease in the population. To identify host and bacterial factors contributing to this process, we examined the time course of colonization
Technology Transfer Automated Retrieval System (TEKTRAN)
Beta-hydroxy-Beta-methylbutyrate (HMB), a leucine catabolite, has been shown to cause increased disease resistance and growth in animal production. A vaccine produced from formalin killed bacteria and concentrated extracellular products of the ARS-98-60 Streptococcus iniae isolate has been used for...
Atlanto-axial subluxation after pyogenic spondylitis of the atlanto-occipital joint.
Tsunoda, Kazuhiko; Iizuka, Haku; Sorimachi, Yasunori; Ara, Tsuyoshi; Nishinome, Masahiro; Takechi, Yasuhiko; Takagishi, Kenji
This report presents a case of atlanto-axial subluxation after treatment of pyogenic spondylitis of the atlanto-occipital joint. A 60-year-old male had 1-month history of neck pain with fever. Magnetic resonance imaging showed inflammation around the odontoid process. Intravenous antibiotic therapy was administrated immediately. After 6 weeks, CRP had returned almost to normal. After 4 months, laboratory data was still normal, but the patient experienced increasing neck pain. Lateral cervical radiography in the neutral position showed instability between C1 and C2. Computed tomography showed a bony union of the atlanto-occipital joint and severe destruction of the atlanto-axial joint on the left side. Transarticular screw fixation for the atlanto-axial joint was performed. A lateral cervical radiograph in the neutral position after surgery showed a solid bony union. Neck pain improved following surgery. We speculate that spondylitis of the atlanto-occipital joint induced a loosening of the transverse ligament and articulation of the atlanto-axial joint. A bony fusion of the atlanto-occipital joint after antibiotic treatment resolved the pyogenic inflammation concentrated stress to the damaged atlanto-axial joint, resulting in further damage. The atlanto-axial instability was finally managed by the insertion of a transarticular screw. PMID:21140176
Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits
Gahukamble, Abhay Deodas; McDowell, Andrew; Post, Virginia; Salavarrieta Varela, Julian; Rochford, Edward Thomas James; Richards, Robert Geoff; Patrick, Sheila
Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure. PMID:24599975
A Genome-Wide Analysis of Small Regulatory RNAs in the Human Pathogen Group A Streptococcus
Nataly Perez; Jeanette Trevińo; Zhuyun Liu; Siu Chun Michael Ho; Paul Babitzke; Paul Sumby; Ramy K. Aziz
The coordinated regulation of gene expression is essential for pathogens to infect and cause disease. A recently appreciated mechanism of regulation is that afforded by small regulatory RNA (sRNA) molecules. Here, we set out to assess the prevalence of sRNAs in the human bacterial pathogen group A Streptococcus (GAS). Genome-wide identification of candidate GAS sRNAs was performed through a tiling
Genetic Classification of Severe Early Childhood Caries by Use of Subtracted DNA Fragments from Streptococcus mutans
Deepak Saxena; Page W. Caufield; Yihong Li; Stuart Brown; Jinmei Song; Robert Norman
Streptococcus mutans is one of several members of the oral indigenous biota linked with severe early childhood caries (S-ECC). Because most humans harbor S. mutans, but not all manifest disease, it has been proposed that the strains of S. mutans associated with S-ECC are genetically distinct from those found in caries-free (CF) children. The objective of this study was to
Identification of Streptococcus suis isolated from swine: proposal for biochemical parameters.
Tarradas, C; Arenas, A; Maldonado, A; Luque, I; Miranda, A; Perea, A
A study was made of the biochemical profiles of 59 strains serotyped as Streptococcus suis, isolated from diseased and clinically healthy pigs. The following parameters are proposed for the identification of the species: Voges-Proskauer negativity, hydrolysis of esculin positivity, trehalose positivity, negativity for growth in 6.5% NaCl, and absence of beta-hemolysis on sheep blood agar. S. suis serotype 2 is negative for hippurate, pyrrolidonylarylamidase, and mannose. PMID:8150982
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus iniae and S. agalactiae are important emergent pathogens that affect many fish species worldwide, especially in warm-water regions. In marine and freshwater systems, these Gram-positive bacteria cause significant economic losses, estimated at hundreds of millions of dollars annually. ...
Pathogenicity of Streptococcus ictaluri to Channel Catfish
Technology Transfer Automated Retrieval System (TEKTRAN)
The infectivity of a Streptococcus ictaluri isolate for fry (0.5 g), fingerling (15 g), and juvenile (55 g) channel catfish (Ictalurus punctatus) was determined by bath immersion and injection infectivity experiments. Channel catfish exposed by immersion were exposed to baths containing 1012, 1011,...
Streptococcus equi subsp. zooepidemicus meningitis in Peru
Guevara, Jose M.; Tilley, Drake H.; Briceno, Jesus A.; Zunt, Joseph R.; Montano, Silvia M.
A 59-year-old man with a history of fever, unsteadiness, hemiparesis, motor aphasia and consciousness disturbance was hospitalized for Streptococcus equi subsp. zooepidemicus meningitis. He denied contact with farm animals, but had a practice of consuming unpasteurized goats' cheese from an uncertain source. PMID:23105024
Revisitingmolecular serotyping of Streptococcus pneumoniae
Background Ninety-two Streptococcus pneumoniae serotypes have been described so far, but the pneumococcal conjugate vaccine introduced in the Brazilian basic vaccination schedule in 2010 covers only the ten most prevalent in the country. Pneumococcal serotype-shifting after massive immunization is a major concern and monitoring this phenomenon requires efficient and accessible serotyping methods. Pneumococcal serotyping based on antisera produced in animals is laborious and restricted to a few reference laboratories. Alternatively, molecular serotyping methods assess polymorphisms in the cps gene cluster, which encodes key enzymes for capsular polysaccharides synthesis in pneumococci. In one such approach, cps-RFLP, the PCR amplified cps loci are digested with an endonuclease, generating serotype-specific fingerprints on agarose gel electrophoresis. Methods In this work, in silico and in vitro approaches were combined to demonstrate that XhoII is the most discriminating endonuclease for cps-RFLP, and to build a database of serotype-specific fingerprints that accommodates the genetic diversity within the cps locus of 92 known pneumococci serotypes. Results The expected specificity of cps-RFLP using XhoII was 76% for serotyping and 100% for serogrouping. The database of cps-RFLP fingerprints was integrated to Molecular Serotyping Tool (MST), a previously published web-based software for molecular serotyping. In addition, 43 isolates representing 29 serotypes prevalent in the state of Minas Gerais, Brazil, from 2007 to 2013, were examined in vitro; 11 serotypes (nine serogroups) matched the respective in silico patterns calculated for reference strains. The remaining experimental patterns, despite their resemblance to their expected in silico patterns, did not reach the threshold of similarity score to be considered a match and were then added to the database. Conclusion The cps-RFLP method with XhoII outperformed the antisera-based and other molecular serotyping methods in regard of the expected specificity. In order to accommodate the genetic variability of the pneumococci cps loci, the database of cps-RFLP patterns will be progressively expanded to include new variant in vitro patterns. The cps-RFLP method with endonuclease XhoII coupled with MST for computer-assisted interpretation of results may represent a relevant contribution to the real time detection of changes in regional pneumococci population diversity in response to mass immunization programs. PMID:26041622
Huge pyogenic cervical cyst with endometriosis, developing 13 years after myomectomy at the lower uterine segment: a case report
Background Surgical site infections are potential complications following open myomectomy. These infections usually develop immediately after the surgery, and are most often located in the myometrium. Pyogenic cervical cysts are rare and have not been previously reported to occur at the site of myomectomy. Case presentation A 41-year-old nulligravida Japanese woman was referred to our hospital with a large cervical cyst (>15 cm in diameter). She had undergone a myomectomy 13 years previously, and the surgical site had extended to the endocervical gland. Standard blood tests did not show any evidence of inflammation. The patient underwent a total abdominal hysterectomy, which revealed that the cyst contained multiple components, including Escherichia coli, old blood, and evidence of endometriosis. A pathological review did not show malignant cells within the cyst. The pyogenic cyst originated from the upper anterior cervix, which was one of the sites involved in the previous myomectomy. Conclusion We reported a huge pyogenic cervical cyst exhibiting signs of endometriosis, in the vicinity of the uterine scar from the open myomectomy. The previous surgery and endometriosis might have contributed to the formation of this rare pyogenic cyst. PMID:25186472
Antimicrobial susceptibility of Streptococcus gallolyticus isolated from humans and animals.
Nomoto, Ryohei; Tien, Le Hong Thuy; Sekizaki, Tsutomu; Osawa, Ro
Susceptibilities to some antimicrobial agents and distribution of genes associated with resistance were examined in a total of 66 Streptococcus gallolyticus isolates and reference strains from various sources. All the tested bacteria were susceptible to vancomycin, penicillin G, and ampicillin. Most of the erythromycin-resistant isolates were observed in human clinical samples. Tetracycline and doxycycline resistance was prevalent in the isolates from human patients, diseased animals, and healthy broiler chickens, while the prevalence was significantly lower in the isolates from healthy mammals. All the isolates resistant to tetracycline possessed tet(M) and/or tet(L) and/or tet(O) genes. However, most isolates from healthy animals, which were susceptible to tetracycline, possessed the above-cited resistance genes, implying the potential ability for resistance under exposure to the corresponding antimicrobial agents. PMID:23883848
Genome of the Bacterium Streptococcus pneumoniae Strain R6
Hoskins, JoAnn; Alborn, William E.; Arnold, Jeffrey; Blaszczak, Larry C.; Burgett, Stanley; DeHoff, Bradley S.; Estrem, Shawn T.; Fritz, Lori; Fu, Dong-Jing; Fuller, Wendy; Geringer, Chad; Gilmour, Raymond; Glass, Jennifer S.; Khoja, Hamid; Kraft, Angelika R.; Lagace, Robert E.; LeBlanc, Donald J.; Lee, Linda N.; Lefkowitz, Elliot J.; Lu, Jin; Matsushima, Patti; McAhren, Scott M.; McHenney, Margaret; McLeaster, Kevin; Mundy, Christopher W.; Nicas, Thalia I.; Norris, Franklin H.; O'Gara, MaryJeanne; Peery, Robert B.; Robertson, Gregory T.; Rockey, Pamela; Sun, Pei-Ming; Winkler, Malcolm E.; Yang, Yong; Young-Bellido, Michelle; Zhao, Genshi; Zook, Christopher A.; Baltz, Richard H.; Jaskunas, S. Richard; Rosteck, Paul R.; Skatrud, Paul L.; Glass, John I.
Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development. PMID:11544234
Evaluation of Melia azedarach extracts against Streptococcus mutans.
Della Bona, Alvaro; Nedel, Fernanda
Although the incidence of caries worldwide has declined in recent years, it is necessary to search for new means to overcome this disease and its microbiological agents. Phytochemistry can become an effective alternative to antibiotics, offering a promising strategy in the prevention and therapy of dental caries. This study aimed to evaluate in vitro the bactericide activity of a bioactive phytocomponent from Melia azedarach against Streptococcus mutans. The crude extract (CEx) from leaves and stem barks of M. azedarach in chloroform, petroleum ether, acetate ethyl, butanol, and aqueous fractions was evaluated using seven different concentrations. Disk diffusion and minimum inhibitory concentration assays were used to evaluate the antibacterial activity. 0.12% chlorhexidine was used as a positive control. The CEx and the petroleum ether fraction from M. azedarach showed significant antibacterial activity against S. mutans, confirming its antibiotic potential. PMID:25069066
Host Responses to Group A Streptococcus: Cell Death and Inflammation
Tsatsaronis, James A.; Walker, Mark J.; Sanderson-Smith, Martina L.
Infections caused by group A Streptococcus (GAS) are characterized by robust inflammatory responses and can rapidly lead to life-threatening disease manifestations. However, host mechanisms that respond to GAS, which may influence disease pathology, are understudied. Recent works indicate that GAS infection is recognized by multiple extracellular and intracellular receptors and activates cell signalling via discrete pathways. Host leukocyte receptor binding to GAS-derived products mediates release of inflammatory mediators associated with severe GAS disease. GAS induces divergent phagocyte programmed cell death responses and has inflammatory implications. Epithelial cell apoptotic and autophagic components are mobilized by GAS infection, but can be subverted to ensure bacterial survival. Examination of host interactions with GAS and consequences of GAS infection in the context of cellular receptors responsible for GAS recognition, inflammatory mediator responses, and cell death mechanisms, highlights potential avenues for diagnostic and therapeutic intervention. Understanding the molecular and cellular basis of host symptoms during severe GAS disease will assist the development of improved treatment regimens for this formidable pathogen. PMID:25165887
Fish Vaccine Development and Use to Prevent Streptococcal Diseases
Technology Transfer Automated Retrieval System (TEKTRAN)
An important pathogen of tilapia, hybrid striped bass and trout raised in intensive aquaculture is Streptococcus sp., a cause of severe economic losses in the fish farming industry. Infected fish experience severe to moderate mortality due to Streptococcus iniae and/or S. agalactiae. The diseased ...
21 CFR 866.3720 - Streptococcus spp. exo-enzyme reagents.
Code of Federal Regulations, 2013 CFR
...2013-04-01 2013-04-01 false Streptococcus spp. exo-enzyme reagents. 866.3720 Section 866.3720 Food and Drugs...Serological Reagents § 866.3720 Streptococcus spp. exo-enzyme reagents. (a) Identification. Streptococcus...
21 CFR 866.3720 - Streptococcus spp. exo-enzyme reagents.
Code of Federal Regulations, 2012 CFR
...2012-04-01 2012-04-01 false Streptococcus spp. exo-enzyme reagents. 866.3720 Section 866.3720 Food and Drugs...Serological Reagents § 866.3720 Streptococcus spp. exo-enzyme reagents. (a) Identification. Streptococcus...
Investigating How Streptococcus Responds to Their Environment: Bringing Together Current Research, a Case Study and Laboratory Investigation †
Quimby, B. Boots; McIver, Kevin S.; Marbach-Ad, Gili; Smith, Ann C.
Understanding the link between course work and unanswered authentic research questions being explored in the research lab is an important goal in undergraduate science teaching. The activity presented here focuses on current research regarding the virulence characteristics of Streptococcus pyogenes particularly targeting the control of sugar uptake regulated via catabolite repression. Students were challenged to formulate a research question and use higher-order thinking skills to analyze data, work collaboratively to solve problems, and pose and test a hypothesis in the laboratory setting. The activity employed an interrupted case study approach using both online and face-to-face settings. The case story and problems were distributed online and were followed by in-class discussions and lab work. Aspects of the activity required independent thinking, as well as collaborative work. Student learning gains were demonstrated via comparison of pre- and postscores on the Host Pathogen Interactions (HPI) concept inventory, results from an end of semester Student Perception Survey, and from analysis of students' work. PMID:23653762
Induction of group A Streptococcus virulence by a human antimicrobial peptide.
Gryllos, Ioannis; Tran-Winkler, Hien J; Cheng, Ming-Fang; Chung, Hachung; Bolcome, Robert; Lu, Wuyuan; Lehrer, Robert I; Wessels, Michael R
Group A streptococci (Streptococcus pyogenes or GAS) freshly isolated from individuals with streptococcal sore throat or invasive ("flesh-eating") infection often grow as mucoid colonies on primary culture but lose this colony appearance after laboratory passage. The mucoid phenotype is due to abundant production of the hyaluronic acid capsular polysaccharide, a key virulence determinant associated with severe GAS infections. These observations suggest that signal(s) from the human host trigger increased production of capsule and perhaps other virulence factors during infection. Here we show that subinhibitory concentrations of the human antimicrobial cathelicidin peptide LL-37 stimulate expression of the GAS capsule synthesis operon (hasABC). Up-regulation is mediated by the CsrRS 2-component regulatory system: it requires a functional CsrS sensor protein and can be antagonized by increased extracellular Mg(2+), the other identified environmental signal for CsrS. Up-regulation was also evident for other CsrRS-regulated virulence genes, including the IL-8 protease PrtS/ScpC and the integrin-like/IgG protease Mac/IdeS, findings that suggest a coordinated GAS virulence response elicited by this antimicrobial immune effector peptide. LL-37 signaling through CsrRS led to a marked increase in GAS resistance to opsonophagocytic killing by human leukocytes, an in vitro measure of enhanced GAS virulence, consistent with increased expression of the antiphagocytic capsular polysaccharide and Mac/IdeS. We propose that the human cathelicidin LL-37 has the paradoxical effect of stimulating CsrRS-regulated virulence gene expression, thereby enhancing GAS pathogenicity during infection. The ability of GAS to sense and respond to LL-37 may explain, at least in part, the unique susceptibility of the human species to streptococcal infection. PMID:18936485
Efficacy of canine influenza virus (H3N8) vaccine to decrease severity of clinical disease after co-challenge with canine influenza virus and Streptococcus equi subsp. Zooepidemicus
Technology Transfer Automated Retrieval System (TEKTRAN)
Since first emerging into the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. Severity of disease is variable, and co-infection by other respiratory pathogens is an impo...
Involvement of Lsp, a Member of the LraI-Lipoprotein Family in Streptococcus pyogenes, in Eukaryotic Cell Adhesion and Internalization
Andrea Elsner; Bernd Kreikemeyer; Andrea Braun-Kiewnick; Barbara Spellerberg; Bettina A. Buttaro; Andreas Podbielski
Three open reading frames (ORFs) were identified by a genome walking strategy in the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591. These ORFs were located between the mga core regulon and the dipeptide permease operon. The deduced amino acid (aa) sequences contained signature sequences indicative of a lipoprotein (306 aa), an intracellular protein (823 aa),
Pyogenic granuloma near the midline of the oral cavity: A series of case reports
Adusumilli, Srikanth; Yalamanchili, Pallavi Samatha; Manthena, Sathish
Pyogenic granuloma (PyG) is a common cause of swelling in the oral cavity during pregnancy and also as an exaggerated response to any minor trauma. The condition is frequently associated with periodontal pain and discomfort, in some cases interfering with mastication and creating esthetic problems. Six patients reported to the Department of Periodontics with gingival overgrowth in the lower anteriors. After recording the details of the patients' oral hygiene status, all the patients were provided initial therapy with scaling and were prescribed analgesics for the reduction of pain and discomfort. After 1 week, surgical excision of the overgrowth was performed and sent for histopathological analysis. The histopathological report is suggestive of PyG. PMID:24872636
21 CFR 866.3740 - Streptococcus spp. serological reagents.
Code of Federal Regulations, 2012 CFR
... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus spp. serological reagents. (a) Identification....
21 CFR 866.3740 - Streptococcus spp. serological reagents.
Code of Federal Regulations, 2014 CFR
... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus spp. serological reagents. (a) Identification....
Risco, David; Fernández-Llario, Pedro; Cuesta, Jesús M; García-Jiménez, Waldo L; Gonçalves, Pilar; Martínez, Remigio; García, Alfredo; Rosales, Rubén; Gómez, Luis; de Mendoza, Javier Hermoso
Streptococcus suis is a recognized pathogen that may cause important diseases in pigs and humans. This microorganism has been repeatedly isolated from wild boar ( Sus scrofa ). However, its health implications for this wild species are still unknown. This article reports a detailed description of a fatal case of septicemia by S. suis affecting a young wild boar. The affected animal, about 15 days old, was found near death and exhibiting neurologic signs at a wild boar estate in southwestern Spain. Postmortem examination showed generalized congestion, brain hemorrhages and lobular pneumonia. Histopathological evaluation demonstrated the presence of meningitis and encephalitis with marked congestion and suppurative bronchopneumonia. Streptococcus suis serotype 2 isolates exhibiting important virulence factors (extracellular factor, muramidase-released protein, and suylisin) were isolated from the affected animal. This study confirms the presence of potentially virulent and zoonotic strains of S. suis in wild boar from Spain. PMID:26056897
Genomics, evolution, and molecular epidemiology of the Streptococcus bovis/Streptococcus equinus complex (SBSEC).
Jans, Christoph; Meile, Leo; Lacroix, Christophe; Stevens, Marc J A
The Streptococcus bovis/Streptococcus equinus complex (SBSEC) is a group of human and animal derived streptococci that are commensals (rumen and gastrointestinal tract), opportunistic pathogens or food fermentation associates. The classification of SBSEC has undergone massive changes and currently comprises 7 (sub)species grouped into four branches based on sequences identities: the Streptococcus gallolyticus, the Streptococcus equinus, the Streptococcus infantarius and the Streptococcus alactolyticus branch. In animals, SBSEC are causative agents for ruminal acidosis, potentially laminitis and infective endocarditis (IE). In humans, a strong association was established between bacteraemia, IE and colorectal cancer. Especially the SBSEC-species S. gallolyticus subsp. gallolyticus is an emerging pathogen for IE and prosthetic joint infections. S. gallolyticus subsp. pasteurianus and the S. infantarius branch are further associated with biliary and urinary tract infections. Knowledge on pathogenic mechanisms is so far limited to colonization factors such as pili and biofilm formation. Certain strain variants of S. gallolyticus subsp. macedonicus and S. infantarius subsp. infantarius are associated with traditional dairy and plant-based food fermentations and display traits suggesting safety. However, due to their close relationship to virulent strains, their use in food fermentation has to be critically assessed. Additionally, implementing accurate and up-to-date taxonomy is critical to enable appropriate treatment of patients and risk assessment of species and strains via recently developed multilocus sequence typing schemes to enable comparative global epidemiology. Comparative genomics revealed that SBSEC strains harbour genomics islands (GI) that seem acquired from other streptococci by horizontal gene transfer. In case of virulent strains these GI frequently encode putative virulence factors, in strains from food fermentation the GI encode functions that are pivotal for strain performance during fermentation. Comparative genomics is a powerful tool to identify acquired pathogenic functions, but there is still an urgent need for more physiological and epidemiological data to understand SBSEC-specific traits. PMID:25233845
Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1
Khare, B.; Krishnan, V.; Rajashankar, K.R.; I-Hsiu, H.; Xin, M.; Ton-That, H.; Narayana, S.V. (Texas-HSC); (Cornell); (UAB)
The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoring of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a 'lid' in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y) motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the 'lid' mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis.
A naturally occurring single amino acid replacement in multiple gene regulator of group A Streptococcus significantly increases virulence.
Sanson, Misu; O'Neill, Brian E; Kachroo, Priyanka; Anderson, Jeff R; Flores, Anthony R; Valson, Chandni; Cantu, Concepcion C; Makthal, Nishanth; Karmonik, Christof; Fittipaldi, Nahuel; Kumaraswami, Muthiah; Musser, James M; Olsen, Randall J
Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype-patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes. PMID:25476528
Antibacterial activity of clove, gall nut methanolic and ethanolic extracts on Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448
Mirpour, Mirsasan; Gholizadeh Siahmazgi, Zohreh; Sharifi Kiasaraie, Masoumeh
Introduction Antimicrobial compounds from herbal sources have good therapeutic potential. In this study, the antibacterial effects of clove and gall nut, methanolic and ethanolic extractions, were evaluated for their effect on Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448, as both the two cause oral diseases. Method The clove and gall nut methanolic and ethanolic extracts were prepared and antibacterial activity was evaluated for S. mutans and S. salivarius in the base of inhibition zone diameter using agar diffusion method. In this part minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were assessed. Results These extracts showed effective antibacterial activity on bacteria. Antibacterial activity of Methanolic extract of clove was more than that of ethanolic extract, and ethanolic extracts of gall nut had antibacterial activity more than that of methanolic extracts. MIC and MBC results for clove methanolic extract were 1.5 mg/ml and 3 mg/ml for S. mutans and 6.25 mg/ml and 12.5 mg/ml for S. salivarius, respectively. These results for clove ethanolic extracts were 12.5 mg/ml and 25 mg/ml for S. mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively. MIC and MBC results for gall nut methanolic extract were 25 mg/ml and 50 mg/ml for S. mutans and 12.5 mg/ml and 25 mg/ml for S. salivarius, respectively. These results for gall nut ethanolic extracts were 3.1 mg/ml and 6.2 mg/ml for S. mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively. Discussion The results showed effective antibacterial activity using clove and gall nut methanolic extracts. If other properties such as tolerance of tissue can also be studied, these extracts can be used as a mouthwash. PMID:25853041
Chemical and botanical characterization of Chilean propolis and biological activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus.
Barrientos, Leticia; Herrera, Christian L; Montenegro, Gloria; Ortega, Ximena; Veloz, Jorge; Alvear, Marysol; Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A
Propolis is a non-toxic natural substance with multiple pharmacological properties including anti-cancer, antioxidant, fungicidal, antibacterial, antiviral, and anti-inflammatory among others. The aim of this study was to determine the chemical and botanical characterization of Chilean propolis samples and to evaluate their biological activity against the cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. Twenty propolis samples were obtained from beekeeping producers from the central and southern regions of Chile. The botanical profile was determined by palynological analysis. Total phenolic contents were determined using colorimetric assays. Reverse phase HPLC and HPLC-MS were used to determine the chemical composition. The minimum inhibitory concentration (MIC) was determined on S. mutans and S. sobrinus. All propolis samples were dominated by structures from native plant species. The characterization by HPLC/MS, evidenced the presence of quercetin, myricetin, kaempferol, rutine, pinocembrin, coumaric acid, caffeic acid and caffeic acid phenethyl ester, that have already been described in these propolis with conventional HPLC. Although all propolis samples inhibited the mutans streptococci growth, it was observed a wide spectrum of action (MIC 0.90 to 8.22 ?g mL(-1)). Given that results it becomes increasingly evident the need of standardization procedures, where we combine both the determination of botanical and the chemical characterization of the extracts. Research conducted to date, describes a promising effectiveness of propolis in the prevention of caries and other diseases of the oral cavity, making it necessary to develop studies to identify and understand the therapeutic targets or mechanisms of molecular action of the various compounds present on them. PMID:24294257
Streptococcus acidominimus infection in a child causing Gradenigo syndrome
Y. Finkelstein; N. Marcus; R. Mosseri; Z. Bar-Sever; B. Z. Garty
Gradenigo syndrome is a rare presentation of acute petrositis. The clinical triad of Gradenigo syndrome consists of acute suppurative otitis media, severe unilateral headache and abducens nerve palsy. We report the first case of Gradenigo syndrome caused by Streptococcus acidominimus, a Gram-positive coccus of the Streptococcus viridans group, which rarely causes deep-seated infection in humans. Conclusion: Gradenigo syndrome may complicate
ComX activity of Streptococcus mutans growing in biofilms
Marcelo B. Aspiras; Richard P. Ellen; Dennis G. Cvitkovitch
In many streptococci, including Streptococcus mutans, genetic competence is regulated by a quorum sensing system mediated by a competence stimulating peptide (CSP) pheromone, encoded by the comC gene. In Streptococcus pneumoniae, a central component of this system is ComX, which acts as an alternative sigma factor to activate competence genes involved in DNA uptake and processing. The quorum sensing system
Differences in Cariogenicity between Fresh Isolates of Streptococcus sobrinus and Streptococcus mutans
J. J. de Soet; C. van Loveren; A. J. Lammens; C. H. E. Homburg; J. M. ten Cate; J. de Graaff
Streptococcus sobrinus is known to possess cariogenic properties in vitro. It can produce acid in large amounts and it has the capacity to adhere to enamel and other surfaces. However, most studies on cariogenicity have been performed with laboratory strains that have been subcultured over long periods of time. Therefore, the cariogenicity and acidogenicity of 9 fresh isolates of both
Streptococcus raffinozactis Orla- Jensen and Hansen, a Group N Streptococcus Found in Raw Milk
The properties of the lactate dehydrogenases, percent guanine plus cytosine in the deoxyribonucleic acid (DNA), and DNA\\/DNA hybridization studies have shown that three strains of group N streptococci do not belong to either Strep- tococcus Zactis or Streptococcus cremoris. The biochemical properties of the three strains were published about 25 years ago, and at that time the strains were not
Graft-versus-host disease, an eight case report and literature review
Ronell Bologna Molina; María Teresa de Jesús; Vega González
Graft versus host disease (GVHD) is a common complication in bone marrow transplant (BMT) patients. It is cha- racterized by systemic and oral cavity alterations. Depending on the timing of lesions, GVHD is classified as acute or chronic. Alterations in the oral cavity are lichenoid reticular lesions, erythema, ulcerations, and xerostomia. Sporadically, mucocele and pyogenic granulomas can be present. Aim:
Treatment of seven cases of chronic granulomatous disease with sulfamethoxazole-trimethoprim (SMX-TMP)
Yohnosuke Kobayashi; Daisuke Amano; Kazuhiro Ueda; Yuji Kagosaki; Tomofusa Usui
Seven male Japanese children with chronic granulomatous disease were given sulfamethoxazole-trimethoprim (SMX-TMP) for recurrent pyogenic infections, most of which had proved difficult to control with other antibiotics. With continuous treatment the children remained free of infections severe enough to necessitate hospitalization, except on one occasion. Serious complications, including hematological disorders, never occurred during therapy and there were no changes in
Group B Streptococcus pili mediate adherence to salivary glycoproteins.
Brittan, Jane L; Nobbs, Angela H
Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia and meningitis, and is responsible for a rising number of severe invasive infections in adults. For all disease manifestations, colonisation is a critical first step. GBS has frequently been isolated from the oropharynx of neonates and adults. However, little is understood about the mechanisms of GBS colonisation at this site. In this study it is shown that three GBS strains (COH1, NEM316, 515) have capacity to adhere to human salivary pellicle. Heterologous expression of GBS pilus island (PI) genes in Lactococcus lactis to form surface-expressed pili demonstrated that GBS PI-2a and PI-1 pili bound glycoprotein-340 (gp340), a component of salivary pellicle. By contrast, PI-2b pili did not interact with gp340. The variation was attributable to differences in capacities for backbone and ancillary protein subunits of each pilus to bind gp340. Furthermore, while GBS strains were aggregated by fluid-phase gp340, this mechanism was not mediated by pili, which displayed specificity for immobilised gp340. Thus pili may enable GBS to colonise the soft and hard tissues of the oropharynx, while evading an innate mucosal defence, with implications for risk of progression to severe diseases such as meningitis and sepsis. PMID:25576026
Investigation of oral ?-streptococcus showing inhibitory activity against pathogens in children with tonsillitis
Isao Fujimori; Rei Goto; Kazuhito Kikushima; Ken-ichi Hisamatsu; Yoshihiko Murakami; Toshihiko Yamada
The incidence of oral ?-streptococcus with inhibitory activity against group A streptococcus, as a defense mechanism against bacterial infection in the oral cavity, was investigated in pediatric individuals with tonsillitis. Infection by group A streptococcus appeared to be common in children, because the detection rate of inhibitory ?-streptococcus in healthy children as well as pediatric patients with tonsillitis was lower
Longitudinal Study of Transmission, Diversity, and Stability of Streptococcus mutans and Streptococcus sobrinus Genotypes in Brazilian Nursery Children
Marlise Inez Klein; Flavia Martao Florio; Antonio Carlos Pereira; JoseFrancisco Hofling; Reginaldo Bruno Goncalves
The aim of this study was to perform a follow-up evaluation of the Streptococcus mutans and Streptococcus sobrinus colonization profile of children's oral cavities, which included the pattern of vertical transmission from mother to child, genotypic diversity, and stability of the strains. The subjects were 16 mother-child pairs, who were monitored for 20 months. Samples of saliva, tongue dorsum, alveolar
Streptococcus iniae sp. nov. , a Beta-Hemolytic Streptococcus Isolated from an Amazon Freshwater Dolphin, Inia geo ffrens is
Evidence is presented for the recognition of a new species of Streptococcus isolated from abscess foci in an Amazon freshwater dolphin, Inia geoffrensis . The organism appears to be immunologically distinct from members of the recognized Lancefield groups of streptococci. Antigens prepared by five different extraction procedures do not react with antisera to Streptococcus groups A to U, whereas antisera
[Streptococcus mutans and dental caries: microbiological aspects].
Zucca, M; Cenna, S; Berzioli, S; Gariglio, M; Fagnoni, V
The central role of Streptococcus mutans in the pathogenesis of caries is universally recognized. In this article we discuss bacterial metabolism relevant to plaque formation and enamel destruction, and review current methods and new prospects in caries prophylaxis: the use of fluorine, possible substitutes for sucrose, active and passive immunoprophylaxis, teeth colonization with non-cariogenic strains of S. mutans. No one of these methods can be considered a definitive solution for every caries problem, but short term major achievements can be reasonably attained by ongoing field research. PMID:2133318
Homocysteine biosynthesis pathways of Streptococcus anginosus.
Yoshida, Yasuo; Negishi, Masahiro; Nakano, Yoshio
A gene (cgs) encoding cystathionine gamma-synthase was cloned from Streptococcus anginosus, and its protein was purified and characterized. The cgs gene and the immediately downstream lcd gene were shown to be cotranscribed as an operon. High-performance liquid chromatography analyses showed that the S. anginosus Cgs not only has cystathionine gamma-synthase activity, but also expresses O-acetylhomoserine sulfhydrylase activity. These results suggest that S. anginosus has the capacity to utilize both the transsulfuration and direct sulfhydrylation pathways for homocysteine biosynthesis. PMID:12725939
Acid tolerance mechanisms utilized by Streptococcus mutans
Matsui, Robert; Cvitkovitch, Dennis
Since its discovery in 1924 by J Clarke, Streptococcus mutans has been the focus of rigorous research efforts due to its involvement in caries initiation and progression. Its ability to ferment a range of dietary carbohydrates can rapidly drop the external environmental pH, thereby making dental plaque inhabitable to many competing species and can ultimately lead to tooth decay. Acid production by this oral pathogen would prove suicidal if not for its remarkable ability to withstand the acid onslaught by utilizing a wide variety of highly evolved acid-tolerance mechanisms. The elucidation of these mechanisms will be discussed, serving as the focus of this review. PMID:20210551
Nasal carriage of Streptococcus pneumoniae serotypes and Staphylococcus aureus in Streptococcus pneumoniae-vaccinated and non-vaccinated young children.
Dukers-Muijrers, N H T M; Stobberingh, E; Beisser, P; Boesten, R C H; Jacobs, P; Hoebe, C J P A
Since the implementation of Streptococcus pneumoniae (SPn) conjugate vaccination (PCV), non-vaccine types have prevailed in invasive pneumococcal disease (IPD), and an increase in Staphylococcus aureus (SA) burden has been suggested. Here, we assess the epidemiology of SA and SPn nasal carriage in 620 children at day-care centres; 141 of these children had received 1-4 PCV7 doses. A higher vaccine dosage was associated with non-vaccine-type SPn carriage. Of all SPn isolates, 45% were PCV7 types, 1% were additional PCV10 types and 22% were the three additional PCV13 types. SA carriage was inversely associated with vaccine-type SPn carriage. SPn serotype 19A showed higher SA co-carriage rates compared to other SPn serotypes. PCV7 implementation does not prevent children from being part of the IPD-related SPn transmission chain. These results contribute to the monitoring of SA- and SPn-related disease and add to the debate on the current national vaccination policy that recently included a change from PCV7 to PCV10. PMID:22687602
Epitopes shared among pioneer oral flora and Streptococcus mutans GbpB
William F. King; Tsute Chen; Ruchele Nogueira; Renata Mattos-Graner; Daniel J. Smith
\\u000a The establishment of microorganisms in emerging oral biofilms of humans is likely to be modulated by a constellation of infant,\\u000a maternal, and microbial factors. We have shown that pioneer microbiota on epithelial surfaces (e.g., Streptococcus mitis, Streptococcus salivarius) and initially erupting dental surfaces (e.g., Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus oralis) induce mucosal SIgA antibody in saliva. The resulting immune
Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin of Trueperella pyogenes.
Preta, Giulio; Lotti, Virginia; Cronin, James G; Sheldon, I Martin
The virulence of many Gram-positive bacteria depends on cholesterol-dependent cytolysins (CDCs), which form pores in eukaryotic cell plasma membranes. Pyolysin (PLO) from Trueperella pyogenes provided a unique opportunity to explore cellular responses to CDCs because it does not require thiol activation. Sublytic concentrations of PLO stimulated phosphorylation of MAPK ERK and p38 in primary stromal cells, and induced autophagy as determined by protein light-chain 3B cleavage. Although, inhibitors of MAPK or autophagy did not affect PLO-induced cytolysis. However, 10 ?M 3-hydroxynaphthalene-2-carboxylic acid-(3,4-dihydroxybenzylidene)-hydrazide (Dynasore), a dynamin guanosine 5'-triphosphatase inhibitor, protected stromal cells against PLO-induced cytolysis as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (85 ± 17% versus 50 ± 9% cell viability), measuring extracellular ATP, and kinetic assays. This was a generalized mechanism because Dynasore also protected HeLa cells against streptolysin O. Furthermore, the effect was reversible, with stromal cell sensitivity to PLO restored within 30 minutes of Dynasore removal. The protective effect of Dynasore was not conferred by dynamin inhibition, induction of ERK phosphorylation, or Dynasore binding to PLO. Rather, Dynasore reduced cellular cholesterol and disrupted plasma membrane lipid rafts, similar to positive control methyl-?-cyclodextrin. Dynasore is a tractable tool to explore the complexity of cholesterol homeostasis in eukaryotic cells and to develop strategies to counter CDCs. PMID:25550455
Prevalence of and risk factors for endogenous endophthalmitis in patients with pyogenic liver abscesses
Park, In Hyung; Jun, Chung Hwan; Wi, Jin Woo; Park, Seon Young; Lee, Wan Sik; Jung, Sook In; Park, Chang Hwan; Joo, Young Eun; Kim, Hyun Soo; Rew, Jong Sun
Background/Aims Although pyogenic liver abscesses (PLAs) can be successfully treated, the visual prognosis of patients with endogenous endophthalmitis (EE) associated with a PLA is poor. Early diagnosis and prompt intervention may salvage useful vision. Therefore, we investigated risk factors for EE in patients with PLA, to facilitate early diagnosis. Methods Data from 626 patients diagnosed with PLA between January 2004 and July 2013 were analyzed retrospectively. Patients were divided into two groups: those with liver abscess-associated endogenous endophthalmitis (LAEE) and non-LAEE. Results The prevalence of EE in PLA patients was 1.92%. The mean age for all patients (373 males, 59.6%) was 62.8 years. Upon multivariate logistic regression, a liver abscess or another systemic infection (odds ratio [OR], 5.52; p = 0.005), an abscess in the right superior segment (OR, 5.26; p = 0.035), and Klebsiella pneumoniae infection (OR, 3.68; p = 0.039), were risk factors for LAEE. The final visual outcomes of patients with LAEE included no light perception in seven, hand motion only in three, and decreased visual acuity in two. Vitrectomy and early intravitreal injections of antibiotics improved visual acuity and preserved useful vision. Conclusions PLA patients with other systemic infections, abscesses in the right superior segment, and K. pneumoniae infection require close monitoring and early intervention to treat LAEE. Intravitreal antibiotic injections or early vitrectomy may salvage useful vision.
Diverse Virulent Pneumophages Infect Streptococcus mitis
Ouennane, Siham; Leprohon, Philippe; Moineau, Sylvain
Streptococcus mitis has emerged as one of the leading causes of bacterial endocarditis and is related to Streptococcus pneumoniae. Antibiotic resistance has also increased among strains of S. mitis and S. pneumoniae. Phages are being reinvestigated as alternatives to antibiotics for managing infections. In this study, the two virulent phages Cp-1 (Podoviridae) and Dp-1 (Siphoviridae), previously isolated from S. pneumoniae, were found to also infect S. mitis. Microbiological assays showed that both pneumophages could not only replicate in S. mitis but also produced more visible plaques on this host. However, the burst size and phage adsorption data were lower in S. mitis as compared to S. pneumoniae. A comparison of the genomes of each phage grown on both hosts produced identical nucleotide sequences, confirming that the same phages infect both bacterial species. We also discovered that the genomic sequence of podophage Cp-1 of the Félix d'Hérelle collection is different than the previously reported sequence and thus renamed SOCP. PMID:25692983
Diverse virulent pneumophages infect Streptococcus mitis.
Ouennane, Siham; Leprohon, Philippe; Moineau, Sylvain
Streptococcus mitis has emerged as one of the leading causes of bacterial endocarditis and is related to Streptococcus pneumoniae. Antibiotic resistance has also increased among strains of S. mitis and S. pneumoniae. Phages are being reinvestigated as alternatives to antibiotics for managing infections. In this study, the two virulent phages Cp-1 (Podoviridae) and Dp-1 (Siphoviridae), previously isolated from S. pneumoniae, were found to also infect S. mitis. Microbiological assays showed that both pneumophages could not only replicate in S. mitis but also produced more visible plaques on this host. However, the burst size and phage adsorption data were lower in S. mitis as compared to S. pneumoniae. A comparison of the genomes of each phage grown on both hosts produced identical nucleotide sequences, confirming that the same phages infect both bacterial species. We also discovered that the genomic sequence of podophage Cp-1 of the Félix d'Hérelle collection is different than the previously reported sequence and thus renamed SOCP. PMID:25692983
MgrA, an Orthologue of Mga, Acts as a Transcriptional Repressor of the Genes within the rlrA Pathogenicity Islet in Streptococcus pneumoniae
Carolyn Hemsley; Elizabeth Joyce; David L. Hava; Amita Kawale; Andrew Camilli
Streptococcus pneumoniae normally resides in the human nasopharynx in a nondisease state. In response to unknown triggers this organism can descend to the lower respiratory tract and\\/or invade the bloodstream. Regulation and activation of virulence genes play essential roles in this process of disease development. Characterization of S. pneumoniae regulatory networks has been a recent area of interest, but despite
Evaluation of the BD MAX GBS assay to detect Streptococcus group B in LIM broth-enriched antepartum vaginal-rectal specimens.
Schwartz, John; Robinson-Dunn, Barbara; Makin, Jacob; Boyanton, Bobby L
The BD MAX GBS real-time polymerase chain reaction assay was evaluated concomitantly with Centers for Disease Control and Prevention-endorsed culture methods to detect Streptococcus group B from LIM broth-enriched antepartum vaginal-rectal specimens. The sensitivity of both methods exceeded 98%. PMID:22480567
Genome Sequence of Avery's Virulent Serotype 2 Strain D39 of Streptococcus pneumoniae and Comparison with That of Unencapsulated Laboratory Strain R6
Joel A. Lanie; Wai-Leung Ng; Krystyna M. Kazmierczak; Tiffany M. Andrzejewski; Tanja M. Davidsen; Kyle J. Wayne; H. Tettelin; J. I. Glass; M. E. Winkler
Streptococcus pneumoniae (pneumococcus) is a leading human respiratory pathogen that causes a variety of serious mucosal and invasive diseases. D39 is an historically important serotype 2 strain that was used in experiments by Avery and coworkers to demonstrate that DNA is the genetic material. Although isolated nearly a century ago, D39 remains extremely virulent in murine infection models and is
Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence
Christopher S. Bates; Chadia Toukoki; Melody N. Neely; Zehava Eichenbaum
Group A streptococcus (GAS) is a common pathogen of the human skin and mucosal surfaces capable of producing a variety of diseases. In this study, we investigated regulation of iron uptake in GAS and the role of a putative transcriptional regulator named MtsR (for Mts repressor) with homology to the DtxR family of metal-dependent regulatory proteins. An mtsR mutant was
Fatal Levofloxacin Failure in Treatment of a Bacteremic Patient Infected with Streptococcus pneumoniae with a Preexisting parC Mutation
M. de Cueto; J. M. Rodriguez; M. J. Soriano; L. Lopez-Cerero; J. Venero; A. Pascual
The fatal outcome of levofloxacin treatment in a patient with bacteremic pneumonia caused by Streptococcus pneumoniae with a preexisting parC mutation is reported. Failure was due to the emergence of a gyrA mutation after 4 days of therapy. Problems encountered in detecting first-step mutation isolates are discussed. CASE REPORTS A 79-year-old man with a history of chronic obstructive lung disease,
Exploration of the host haemostatic system by Group A Streptococcus: implications in searching for novel antimicrobial therapies
Sun, Hongmin
Summary The haemostatic system is heavily involved in the host response to infection. A number of host haemostatic factors, notably plasminogen and fibrinogen have been reported to bind and interact with various bacterial proteins. This review summarises the roles of host haemostatic factors such as plasminogen, factor V and fibrinogen in host defence against group A streptococcus infection and discusses the potential of targeting the host haemostatic system for therapeutic intervention against infectious diseases. PMID:21781255
Persistence of the Oral Probiotic Streptococcus salivarius M18 Is Dose Dependent and Megaplasmid Transfer Can Augment Their Bacteriocin Production and Adhesion Characteristics
Burton, Jeremy P.; Wescombe, Philip A.; Macklaim, Jean M.; Chai, Melissa H. C.; MacDonald, Kyle; Hale, John D. F.; Tagg, John; Reid, Gregor; Gloor, Gregory B.; Cadieux, Peter A.
Bacteriocin-producing probiotic Streptococcus salivarius M18 offers beneficial modulatory capabilities within the oral microbiome, apparently through potent inhibitory activity against potentially deleterious bacteria, such as Streptococcus pyogenes. The oral cavity persistence of S. salivarius M18 was investigated in 75 subjects receiving four different doses for 28 days. Sixty per cent of the subjects already had some inhibitor-producing S. salivarius in their saliva prior to probiotic intervention. Strain M18's persistence was dependent upon the dose, but not the period of administration. Culture analysis indicated that in some individuals the introduced strain had almost entirely replaced the indigenous S. salivarius, though the total numbers of the species did not increase. Selected subjects showing either high or low probiotic persistence had their salivary populations profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Analysis indicated that while certain bacterial phenotypes were markedly modulated, the overall composition of the oral microbiome was not modified by the probiotic treatment. Megaplasmids encoding bacteriocins and adhesion factors were transferred in vitro to generate a transconjugant S. salivarius exhibiting enhanced antimicrobial production and binding capabilities to HEp-2 cells. Since no widespread perturbation of the existing indigenous microbiota was associated with oral instillation and given its antimicrobial activity against potentially pathogenic streptococci, it appears that application of probiotic strain M18 offers potential low impact alternative to classical antibiotic prophylaxis. For candidate probiotic strains having relatively poor antimicrobial or adhesive properties, unique derivatives displaying improved probiotic performance may be engineered in vitro by megaplasmid transfer. PMID:23785463
Interactions between Oral Bacteria: Inhibition of Streptococcus mutans Bacteriocin Production by Streptococcus gordonii
Bing-Yan Wang; Howard K. Kuramitsu
Received 28 May 2004\\/Accepted 25 August 2004 Streptococcus mutans has been recognized as an important etiological agent in human dental caries. Some strains of S. mutans also produce bacteriocins. In this study, we sought to demonstrate that bacteriocin production by S. mutans strains GS5 and BM71 was mediated by quorum sensing, which is dependent on a competence-stimulating peptide (CSP) signaling
Recent advances in our understanding of Streptococcus pneumoniae infection
Anderson, Ronald
A number of significant challenges remain with regard to the diagnosis, treatment, and prevention of infections with Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of community-acquired pneumonia. Although this infection is documented to be extremely common in younger children and in older adults, the burden of pneumonia it causes is considerably underestimated, since the incidence statistics are derived largely from bacteremic infections, because they are easy to document, and yet the greater burden of pneumococcal pneumonias is non-invasive. It has been estimated that for every bacteremic pneumonia that is documented, three non-bacteremic infections occur. Management of these infections is potentially complicated by the increasing resistance of the isolates to the commonly used antibiotics. Furthermore, it is well recognized that despite advances in medical care, the mortality of bacteremic pneumococcal pneumonia has remained largely unchanged over the past 50 years and averages approximately 12%. Much recent research interest in the field of pneumococcal infections has focused on important virulence factors of the organism, on improved diagnostic and prognostication tools, on defining risk factors for death, on optimal treatment strategies involving both antibiotics and adjunctive therapies, and on disease prevention. It is hoped that through these endeavors the outlook of pneumococcal infections will be improved. PMID:25343039
Small regulatory RNAs in Streptococcus pneumoniae: discovery and biological functions
Wilton, Joana; Acebo, Paloma; Herranz, Cristina; Gómez, Alicia; Amblar, Mónica
Streptococcus pneumoniae is a prominent human pathogen responsible for many severe diseases and the leading cause of childhood mortality worldwide. The pneumococcus is remarkably adept at colonizing and infecting different niches in the human body, and its adaptation to dynamic host environment is a central aspect of its pathogenesis. In the last decade, increasing findings have evidenced small RNAs (sRNAs) as vital regulators in a number of important processes in bacteria. In S. pneumoniae, a small antisense RNA was first discovered in the pMV158 plasmid as a copy number regulator. More recently, genome-wide screens revealed that the pneumococcal genome also encodes multiple sRNAs, many of which have important roles in virulence while some are implicated in competence control. The knowledge of the sRNA-mediated regulation in pneumococcus remains very limited, and future research is needed for better understanding of functions and mechanisms. Here, we provide a comprehensive summary of the current knowledge on sRNAs from S. pneumoniae, focusing mainly on the trans-encoded sRNAs. PMID:25904932
Bacteriostatic effect of copaiba oil (Copaifera officinalis) against Streptococcus mutans.
Pieri, Fábio Alessandro; Mussi, Maria Carolina Martins; Fiorini, Joăo Evangelista; Moreira, Maria Aparecida Scatamburlo; Schneedorf, José Mauricio
This study evaluated the inhibitory activity of copaiba oil (Copaifera officinalis against the cariogenic microorganism, Streptococcus mutans. For such purpose, a minimum inhibition concentration test of copaiba oil against S. mutans was performed, using the serial dilution in broth technique, with a negative control, a positive control (0.12% chlorhexidine) and a 10% copaíba oil solution as a test. A minimum bactericidal concentration test with tubes presenting microbial inhibition was also conduced. In the minimum inhibitory concentration test, copaiba oil showed inhibition of bacterial growth at all concentrations tested up to 0.78 µL/mL of the 10% copaiba oil solution in the broth. In addition, the negative control had no inhibition, and the 0.12% chlorhexidine solution was effective up to 6.25 µL/mL in the broth. Copaiba oil showed a bacteriostatic activity against S. mutans at low concentrations, and could be a an option of phytotherapic agent to be used against cariogenic bacteria in the prevention of caries disease. PMID:22460312
Analysis of an outbreak of Streptococcus uberis mastitis.
Zadoks, R N; Allore, H G; Barkema, H W; Sampimon, O C; Gröhn, Y T; Schukken, Y H
An outbreak of Streptococcus uberis mastitis was described to gain insight into the dynamics of Strep. uberis infections at a herd level. Data were obtained from a longitudinal observational study on a commercial Dutch dairy farm with good udder health management. Quarter milk samples for bacteriological culture were routinely collected at 3-wk intervals from all lactating animals (n = 95 +/- 5). Additional samples were collected at calving, clinical mastitis, dry-off, and culling. During the 78-wk observation period, 54 Strep. uberis infections were observed. The majority of infections occurred during a 21-wk period that constituted the disease outbreak. The incidence rate was higher in quarters that had recovered from prior Strep. uberis infection than in quarters that had not experienced Strep. uberis infection before. The incidence rate of Strep. uberis infection did not differ between quarters that were infected with other pathogens compared with quarters that were not infected with other pathogens. The expected number of new Strep. uberis infections per 3-wk interval was described by means of a Poisson logistic regression model. Significant predictor variables in the model were the number of existing Strep. uberis infections in the preceding time interval (shedders), phase of the study (early phase vs. postoutbreak phase), and prior infection status of quarters with respect to Strep. uberis, but not infection status with respect to other pathogens. Results suggest that contagious transmission may have played a role in this outbreak of Strep. uberis mastitis. PMID:11286411
Biofilm Formation Avoids Complement Immunity and Phagocytosis of Streptococcus pneumoniae
Domenech, Mirian; Ramos-Sevillano, Elisa; García, Ernesto
Streptococcus pneumoniae is a frequent member of the microbiota of the human nasopharynx. Colonization of the nasopharyngeal tract is a first and necessary step in the infectious process and often involves the formation of sessile microbial communities by this human pathogen. The ability to grow and persist as biofilms is an advantage for many microorganisms, because biofilm-grown bacteria show reduced susceptibility to antimicrobial agents and hinder recognition by the immune system. The extent of host protection against biofilm-related pneumococcal disease has not been determined yet. Using pneumococcal strains growing as planktonic cultures or as biofilms, we have investigated the recognition of S. pneumoniae by the complement system and its interactions with human neutrophils. Deposition of C3b, the key complement component, was impaired on S. pneumoniae biofilms. In addition, binding of C-reactive protein and the complement component C1q to the pneumococcal surface was reduced in biofilm bacteria, demonstrating that pneumococcal biofilms avoid the activation of the classical complement pathway. In addition, recruitment of factor H, the downregulator of the alternative pathway, was enhanced by S. pneumoniae growing as biofilms. Our results also show that biofilm formation diverts the alternative complement pathway activation by a PspC-mediated mechanism. Furthermore, phagocytosis of pneumococcal biofilms was also impaired. The present study confirms that biofilm formation in S. pneumoniae is an efficient means of evading both the classical and the PspC-dependent alternative complement pathways the host immune system. PMID:23649097
Molecular typing of Streptococcus agalactiae isolates from fish
Technology Transfer Automated Retrieval System (TEKTRAN)
The genetic variability among Streptococcus agalactiae isolates recovered from fish was characterized using single-stranded conformation polymorphisms (SSCP) analysis of the intergenic spacer region (ISR), and amplified fragment length polymorphism (AFLP) fingerprinting. A total of 49 S. agalactiae ...
Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus
Nizet, Victor
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .267 Pediatric autoimmune neuropsychiatric disorders associated w
Detection of tetracycline resistance in Streptococcus pneumoniae.
Stewart, S M; Anderson, M E; Malcolm, M G
Bacteriological details are given of a patient with chronic purulent bronchitis, who was being followed up during a survey of relapse in chronic bronchitis. A strain of Streptococcus pneumoniae, serotype 10, was isolated from the sputum over a period of six months, followed by a type 47A strain and later a type 28 strain. The patient was receiving prophylactic treatment with tetracycline throughout. The type 10 strain was sensitive to tetracycline in vitro by both the disc diffusion and doubling dilution sensitivity tests and mice infected with this strain were protected by tetracycline. In contrast, both the type 47A and type 28 strains were sensitive by the disc diffusion technique, but showed a low degree of tetracycline resistance by the doubling dilution method; mice infected with both these strains were not protected by tetracycline. PMID:1123446
Group A Streptococcus invasive infections: a review
Weiss, Karl A.; Laverdičre, Michel
The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide, and there is no obvious explanation for this phenomenon. In 1993, a working group on severe GAS infections was established to define accurately what constitutes an invasive infection. Three types of infection are particularly feared: necrotizing fasciitis, myositis and a newly defined entity, named streptococcal toxic shock syndrome (STSS) because of a certain analogy with its staphylococcal counterpart. GAS produces many toxins responsible for its clinical manifestations. Some of them, labelled streptococcal pyrogenic exotoxins, have been characterized as superantigens. These proteins play a key role in initiating the immune response to GAS and are mostly responsible for the precipitous course of invasive infections. Death rates are high in streptococcal invasive infections, ranging from about 20% for necrotizing fasciitis to almost 100% for myositis. Therapy consists mainly of high doses of antibiotic combinations, aggressive surgery, and intravenous administration of immunoglobulins for STSS. PMID:9030079
Conditions to enhance transfection in Streptococcus pneumoniae.
Serratosa, C; López, R; García, E; Ronda, C
Enhancement of transfection in the wild-type strain of Streptococcus pneumoniae, which contains normal levels of nucleases, can be achieved by a careful control of the components of the medium. Protection of the donor DNA against the degradation by the nucleases present at the surface of the cell during the adsorption to the physiologically competent bacteria is a necessary condition to obtain an enhanced transfection. Using [3H]thymidine-labeled Dp-4 DNA we have found that maximal levels of DNA uptake and a remarkable stimulation in genetic transfection were obtained in the presence of calcium ions. Concentrations of magnesium ions higher than 2 mM stimulated the extracellular degradation of the donor DNA and inhibited transfection. PMID:6532007
Autolytic defective mutant of Streptococcus faecalis.
Cornett, J B; Redman, B E; Shockman, G D
Properties of a variant of Streptococcus faecalis ATCC 9790 with defective cellular autolysis are described. The mutant strain was selected as a survivor from a mutagenized cell population simultaneously challenged with two antibiotics which inhibit cell wall biosynthesis, penicillin G and cycloserine. Compared to the parental strain, the mutant strain exhibited: (i) a thermosensitive pattern of cellular autolysis; (ii) an autolytic enzyme activity that had only a slightly increased thermolability when tested in solution in the absence of wall substrate; and (iii) an isolated autolysin that had hydrolytic activity on isolated S. faecalis wall substrate indistinguishable from that of the parental strain, but that was inactive when tested on walls of Micrococcus lysodeikticus as a substrate. These data indicate an alteration in the substrate specificity of the autolytic enzyme of the mutant which appears to result from the synthesis of an altered form of autolytic enzyme. PMID:415045
Ribosomal Mutations in Streptococcus pneumoniae Clinical Isolates
Pihlajamäki, Marja; Kataja, Janne; Seppälä, Helena; Elliot, John; Leinonen, Maija; Huovinen, Pentti; Jalava, Jari
Eleven clinical isolates of Streptococcus pneumoniae, isolated in Finland during 1996 to 2000, had an unusual macrolide resistance phenotype. They were resistant to macrolides and streptogramin B but susceptible, intermediate, or low-level resistant to lincosamides. No acquired macrolide resistance genes were detected from the strains. The isolates were found to have mutations in domain V of the 23S rRNA or ribosomal protein L4. Seven isolates had an A2059C mutation in two to four out of the four alleles encoding the 23S rRNA, two isolates had an A2059G mutation in two alleles, one isolate had a C2611G mutation in all four alleles, and one isolate had a 69GTG71-to-69TPS71 substitution in ribosomal protein L4. PMID:11850244
Brainstem infarcts as an early manifestation of streptococcus anginosus meningitis
Sung B. Lee; Lyell K. Jones; Caterina Giannini
Background and Purpose: Vasculitis and infarcts are well-established sequelae of bacterial meningitis. However, early large-vessel involvement is\\u000a rare, particularly within the brainstem. There has been one previous case report of a young male who presented with pontine\\u000a infarct as an early manifestation of Streptococcus milleri meningitis. We present another case of brainstem infarction associated with meningitis caused by Streptococcus anginosus
From nose to lung: the regulation behind Streptococcus pneumoniae virulence factors
Hava, David L.; LeMieux, Julianna; Camilli, Andrew
Summary Streptococcus pneumoniae probably possesses a redundant set of factors required for colonization of the nasopharynx and invasive disease, because of its strict relationship with its human host and relatively small genome size (~2.1 Mb). Nevertheless, transcriptional regulation of genes encoding factors required for in vivo growth is predicted to be important on two fronts: in the transition from carriage to invasive disease and within different microniches of the nasopharynx. The importance of both serotype-specific and host tissue-specific virulence factors during infection and disease has been highlighted by the recent identification of novel virulence factors in this organism coupled with the release of complete genome sequences from two strains. These studies add to the foundation of knowledge of classical S. pneumoniae virulence factors such as polysaccharide capsule and pneumolysin, which have well-documented roles in pathogenesis PMID:14622402
Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus
Smeesters, Pierre R.; Frost, Hannah R. C.; Steer, Andrew C.
Group A streptococcus (GAS) is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates.
Identification and characterization of a surface protein-releasing activity in Streptococcus mutans and other pathogenic streptococci.
Lee, S F
Surface proteins of Streptococcus mutans have been reported to be released into the culture filtrate at concentrations that vary with the growth conditions. The reason for this is not clear. The present study attempts to investigate the mechanism of the protein release. The results showed that whole cells and raffinose-stabilized protoplasts of S. mutans NG8, when incubated in buffers, were capable of releasing their surface proteins in a pH-dependent manner with optimal release at pH 5 to 6. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the released proteins were very complex. Two proteins, adhesin P1, which has been previously shown to interact with a human salivary agglutinin, and glucosyltransferase have been identified among the released proteins. The release of adhesin P1 and other proteins was found to be inhibited by heat, Cu2+,Zn2+, and thiol-blocking reagents. The inhibition by heat and Cu2+ was irreversible, whereas that by the thiol-blocking reagents was reversible. EDTA, phenylmethylsulfonyl fluoride, and N-p-tosyl-L-lysyl-chloromethyl ketone had no effect on the release of P1, indicating that the release was probably not due to proteolytic activity. Adhesin P1 from Cu(2+)-inactivated S. mutans NG8 protoplasts could be released by mixing with fresh whole cells and protoplasts, but not the culture filtrate, of a P1-negative mutant of NG8, suggesting that the enzyme is located on the cell surface. This P1-releasing activity was also detected in two other strains of S. mutans and one strain each of S. gordonii, S. agalactiae, S. pneumoniae, and S. pyogenes. The biological role(s) of this enzyme activity remains to be determined. However, owing to its ability to release virulent surface proteins from the cell, it may play an important role in cell surface modulation among the pathogenic streptococci. Images PMID:1398915
Cow- and quarter-level risk factors for Streptococcus uberis and Staphylococcus aureus mastitis.
Zadoks, R N; Allore, H G; Barkema, H W; Sampimon, O C; Wellenberg, G J; Gröhn, Y T; Schukkent, Y H
This study was designed to identify risk factors for intramammary infections with Streptococcus uberis and Staphylococcus aureus under field conditions. An 18-mo survey with sampling of all quarters of all lactating cows at 3-wk intervals was carried out in three Dutch dairy herds with medium bulk milk somatic cell count (200,000 to 300,000 cells/ml). Quarter milk samples were used for bacteriology and somatic cell counting. Data on parity, lactation stage, and bovine herpesvirus 4-serology were recorded for each animal. During the last year of the study, body condition score, and teat-end callosity scores were recorded at 3-wk intervals. A total of 93 new infections with Strep. uberis were detected in 22,665 observations on quarters at risk for Strep. uberis infection, and 100 new infections with Staph. aureus were detected in 22,593 observations on quarters at risk for Staph. aureus infection. Multivariable Poisson regression analysis with clustering at herd and cow level was used to identify risk factors for infection. Rate of infection with Strep. uberis was lower in first- and second-parity cows than in older cows, and depended on stage of lactation in one herd. Quarters that were infected with Arcanobacterium pyogenes or enterococci, quarters that had recovered from Strep. uberis- or Staph. aureus-infection in the past, and quarters that were exposed to another Strep. uberis infected quarter in the same cow had a higher rate of Strep. uberis infection. Teat-end callosity and infection with coagulase-negative staphylococci or corynebacteria were not significant as risk factors. Rate of Staph. aureus infection was higher in bovine herpesvirus 4-seropositive cows, in right quarters, in quarters that had recovered from Staph. aureus or Strep. uberis infection, in quarters exposed to other Staph. aureus infected quarters in the same cow, and in quarters with extremely callused teat ends. Infection with coagulase-negative staphylococci was not significant as a risk factor. The effect of infection with corynebacteria on rate of infection with Staph. aureus depended on herd, stage of lactation, and teat-end roughness. Herd level prevalence of Strep. uberis or Staph. aureus, and low quarter milk somatic cell count were not associated with an increased rate of infection for Strep. uberis or Staph. aureus. PMID:11814021
Development of Primer Sets for Loop-Mediated Isothermal Amplification that Enables Rapid and Specific Detection of Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae.
Wang, Deguo; Liu, Yanhong
Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae are the three main pathogens causing bovine mastitis, with great losses to the dairy industry. Rapid and specific loop-mediated isothermal amplification methods (LAMP) for identification and differentiation of these three pathogens are not available. With the 16S rRNA gene and 16S-23S rRNA intergenic spacers as targets, four sets of LAMP primers were designed for identification and differentiation of S. dysgalactiae, S. uberis and S. agalactiae. The detection limit of all four LAMP primer sets were 0.1 pg DNA template per reaction, the LAMP method with 16S rRNA gene and 16S-23S rRNA intergenic spacers as the targets can differentiate the three pathogens, which is potentially useful in epidemiological studies. PMID:26016433
Development of Primer Sets for Loop-Mediated Isothermal Amplification that Enables Rapid and Specific Detection of Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae
Wang, Deguo; Liu, Yanhong
Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae are the three main pathogens causing bovine mastitis, with great losses to the dairy industry. Rapid and specific loop-mediated isothermal amplification methods (LAMP) for identification and differentiation of these three pathogens are not available. With the 16S rRNA gene and 16S-23S rRNA intergenic spacers as targets, four sets of LAMP primers were designed for identification and differentiation of S. dysgalactiae, S. uberis and S. agalactiae. The detection limit of all four LAMP primer sets were 0.1 pg DNA template per reaction, the LAMP method with 16S rRNA gene and 16S-23S rRNA intergenic spacers as the targets can differentiate the three pathogens, which is potentially useful in epidemiological studies. PMID:26016433
Untangling the Web of Systemic Autoinflammatory Diseases
Rigante, Donato; Lopalco, Giuseppe; Vitale, Antonio; Lucherini, Orso Maria; Caso, Francesco; De Clemente, Caterina; Molinaro, Francesco; Messina, Mario; Costa, Luisa; Atteno, Mariangela; Laghi-Pasini, Franco; Lapadula, Giovanni; Galeazzi, Mauro; Iannone, Florenzo; Cantarini, Luca
The innate immune system is involved in the pathophysiology of systemic autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by dysregulated production of proinflammatory cytokines, such as interleukin-1? and tumor necrosis factor-?, in which autoreactive T-lymphocytes and autoantibodies are indeed absent. A widely deranged innate immunity leads to overactivity of proinflammatory cytokines and subsequent multisite inflammatory symptoms depicting various conditions, such as hereditary periodic fevers, granulomatous disorders, and pyogenic diseases, collectively described in this review. Further research should enhance our understanding of the genetics behind SAIDs, unearth triggers of inflammatory attacks, and result in improvement for their diagnosis and treatment. PMID:25132737
Susceptibility of Porphyromonas gingivalis and Streptococcus mutans to Antibacterial Effect from Mammea americana
Herrera Herrera, Alejandra; Franco Ospina, Luis; Fang, Luis; Díaz Caballero, Antonio
The development of periodontal disease and dental caries is influenced by several factors, such as microorganisms of bacterial biofilm or commensal bacteria in the mouth. These microorganisms trigger inflammatory and immune responses in the host. Currently, medicinal plants are treatment options for these oral diseases. Mammea americana extracts have reported antimicrobial effects against several microorganisms. Nevertheless, this effect is unknown against oral bacteria. Therefore, the aim of this study was to evaluate the antibacterial effect of M. americana extract against Porphyromonas gingivalis and Streptococcus mutans. For this, an experimental study was conducted. Ethanolic extract was obtained from seeds of M. americana (one oil phase and one ethanolic phase). The strains of Porphyromonas gingivalis ATCC 33277 and Streptococcus mutans ATCC 25175 were exposed to this extract to evaluate its antibacterial effect. Antibacterial activity was observed with the two phases of M. americana extract on P. gingivalis and S. mutans with lower MICs (minimum inhibitory concentration). Also, bactericidal and bacteriostatic activity was detected against S. mutans, depending on the concentration of the extract, while on M. americana extract presented only bacteriostatic activity against P. gingivalis. These findings provide important and promising information allowing for further exploration in the future. PMID:24864137
Naik, Haley B.; Cowen, Edward W.
SYNOPSIS The inflammatory pustular dermatoses constitute a spectrum of non-infectious conditions ranging from localized involvement to generalized disease with associated acute systemic inflammation and multi-organ involvement. Despite the variability in extent and severity of cutaneous presentation, each of these diseases is characterized by non-infectious neutrophilic intra-epidermal microabscesses. Many share systemic findings including fever, elevated inflammatory markers, inflammatory bowel disease and/or osteoarticular involvement, suggesting potential common pathogenic links (Figure 1). The recent discoveries of several genes responsible for heritable pustular diseases have revealed a distinct link between pustular skin disease and regulation of innate immunity. These genetic advances have led to a deeper exploration of common pathways in pustular skin disease and offer the potential for a new era of biologic therapy which targets these shared pathways. This chapter provides a new categorization of inflammatory pustular dermatoses in the context of recent genetic and biologic insights. We will discuss recently-described monogenic diseases with pustular phenotypes, including deficiency of IL-1 receptor antagonist (DIRA), deficiency of the IL-36 receptor antagonist (DITRA), CARD14-associated pustular psoriasis (CAMPS), and pyogenic arthritis, pyoderma gangrenosum, acne (PAPA). We will then discuss how these new genetic advancements may inform how we view previously described pustular diseases, including pustular psoriasis and its clinical variants, with a focus on historical classification by clinical phenotype. PMID:23827244
Energy condition affects fermentation rate of Streptococcus bovis without changing fermentation pattern
Boyer, Edmond
Energy condition affects fermentation rate of Streptococcus bovis without changing fermentation fermentation patterns are unclear. Streptococcus bovis is a major ruminal bacteria, produces acetate, lactate condition would affect the fermentation pattern by S. bovis. Carbonylcyanide m-chlorophenylhydrazone (CCCP
Five-Year Analysis of Antimicrobial Susceptibility of the Streptococcus milleri Group
A. Limia; M. L. Jiménez; T. Alarcón; M. López-Brea
Susceptibility to 17 antibiotics was studied in 180 strains of the Streptococcus milleri group (88 Streptococcus anginosus, 63 Streptococcus constellatus, and 29 Streptococcus intermedius) isolated over a 5-year period. Minimum inhibitory concentrations of penicillin were in the intermediate range for 5.6% of\\u000a the strains. Resistance to erythromycin and clindamycin was found in 17.1% and 16.6% of the isolates, respectively. A
Phenotypic Heterogeneity of Genomically-Diverse Isolates of Streptococcus mutans
Palmer, Sara R.; Miller, James H.; Abranches, Jacqueline; Zeng, Lin; Lefebure, Tristan; Richards, Vincent P.; Lemos, José A.; Stanhope, Michael J.; Burne, Robert A.
High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease. PMID:23613838
Phenotypic heterogeneity of genomically-diverse isolates of Streptococcus mutans.
Palmer, Sara R; Miller, James H; Abranches, Jacqueline; Zeng, Lin; Lefebure, Tristan; Richards, Vincent P; Lemos, José A; Stanhope, Michael J; Burne, Robert A
High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease. PMID:23613838
?-Phosphoglucomutase contributes to aciduricity in Streptococcus mutans
Buckley, Andrew A.; Faustoferri, Roberta C.
Streptococcus mutans encounters an array of sugar moieties within the oral cavity due to a varied human diet. One such sugar is ?-d-glucose 1-phosphate (?DG1P), which must be converted to glucose 6-phosphate (G6P) before further metabolism to lactic acid. The conversion of ?DG1P to G6P is mediated by ?-phosphoglucomutase, which has not been previously observed in any oral streptococci, but has been extensively characterized and the gene designated pgmB in Lactococcus lactis. An orthologue was identified in S. mutans, SMU.1747c, and deletion of the gene resulted in the inability of the deletion strain to convert ?DG1P to G6P, indicating that SMU.1747c is a ?-phosphoglucomutase and should be designated pgmB. In this study, we sought to characterize how deletion of pgmB affected known virulence factors of S. mutans, specifically acid tolerance. The ?pgmB strain showed a decreased ability to survive acid challenge. Additionally, the strain lacking ?-phosphoglucomutase had a diminished glycolytic profile compared with the parental strain. Deletion of pgmB had a negative impact on the virulence of S. mutans in the Galleria mellonella (greater wax worm) animal model. Our results indicate that pgmB plays a role at the juncture of carbohydrate metabolism and virulence. PMID:24509501
A novel iron transporter in Streptococcus iniae.
Wang, J; Zou, L L; Li, A X
Streptococcus iniae is a major pathogen that results in considerable economic loss to fish farms. Restricted availability of iron is a huge obstacle to survival for pathogenic bacteria during infection, and iron acquisition is important in bacterial virulence. In this study, S. iniae HD-1 was shown not to produce siderophores (low-molecular-weight compounds) but rather to require iron-containing proteins for growth under iron-restricted conditions. The adenosine triphosphate (ATP)-binding-cassette (ABC) transporter system (ftsABCD), which is cotranscribed by four downstream genes, namely, ftsA, ftsB, ftsC and ftsD, was identified as responsible for haem utilization of S. iniae. Analysis of the corresponding recombinant protein, FtsB, indicated that it is a putative lipoprotein which plays a role in haem utilization and is produced in vivo during infection with S. iniae HD-1, and therefore may be a potential candidate antigen for a streptococcal vaccine. PMID:24102320
Peptide pheromone signaling in Streptococcus and Enterococcus
Cook, Laura C.; Federle, Michael J.
Intercellular chemical signaling in bacteria, commonly referred to as quorum sensing (QS), relies on the production and detection of compounds known as pheromones to elicit coordinated responses among members of a community. Pheromones produced by Gram-positive bacteria are comprised of small peptides. Based on both peptide structure and sensory system architectures, Gram-positive bacterial signaling pathways may be classified into one of four groups with a defining hallmark: cyclical peptides of the Agr type, peptides that contain Gly-Gly processing motifs, sensory systems of the RNPP family, or the recently characterized Rgg-like regulatory family. The recent discovery that Rgg family members respond to peptide pheromones increases substantially the number of species in which QS is likely a key regulatory component. These pathways control a variety of fundamental behaviors including conjugation, natural competence for transformation, biofilm development, and virulence factor regulation. Overlapping QS pathways found in multiple species and pathways that utilize conserved peptide pheromones provide opportunities for interspecies communication. Here we review pheromone signaling identified in the genera Enterococcus and Streptococcus, providing examples of all four types of pathways. PMID:24118108
Streptococcus mutans dextransucrase: requirement for primer dextran.
Germaine, G R; Chludzinski, A M; Schachtele, C F
Dextran stimulation (priming) of the dextransucrase (EC 220.127.116.11) from Streptococcus mutans strain 6715 was studied. The dextransucrase activity in supernatant fluids from glucose-grown cultures was shown to be partially primer dependent. During extended storage at 4 C the enzyme retained its activity. However, the ability to make dextran became increasingly primer dependent. Hydroxylapatite-chromatographed enzyme preparations were completely dependent upon added dextran for rapid synthesis of methanol-insoluble glucan from sucrose. Half-maximal stimulation of new dextran synthesis occurred with dextran at a concentration of 2 to 3 muM and with a molecular weight of about 2,600. Neither glycogen, amylose, inulin, nor isomaltose functioned as primer. Studies with the dextransucrase activities detectable by in situ assay in polyacrylamide gels subjected to electrophoresis under nondenaturing conditions revealed that the major activity was detectable in the presence of sucrose alone and was stimulated by addition of primer dextran. The minor activity was only detected when primer dextran was present. Homogeneous preparations of both enzymes contained 30 to 40% carbohydrate. PMID:4423486
Genome of the Opportunistic Pathogen Streptococcus sanguinis? †
Xu, Ping; Alves, Joao M.; Kitten, Todd; Brown, Arunsri; Chen, Zhenming; Ozaki, Luiz S.; Manque, Patricio; Ge, Xiuchun; Serrano, Myrna G.; Puiu, Daniela; Hendricks, Stephanie; Wang, Yingping; Chaplin, Michael D.; Akan, Doruk; Paik, Sehmi; Peterson, Darrell L.; Macrina, Francis L.; Buck, Gregory A.
The genome of Streptococcus sanguinis is a circular DNA molecule consisting of 2,388,435 bp and is 177 to 590 kb larger than the other 21 streptococcal genomes that have been sequenced. The G+C content of the S. sanguinis genome is 43.4%, which is considerably higher than the G+C contents of other streptococci. The genome encodes 2,274 predicted proteins, 61 tRNAs, and four rRNA operons. A 70-kb region encoding pathways for vitamin B12 biosynthesis and degradation of ethanolamine and propanediol was apparently acquired by horizontal gene transfer. The gene complement suggests new hypotheses for the pathogenesis and virulence of S. sanguinis and differs from the gene complements of other pathogenic and nonpathogenic streptococci. In particular, S. sanguinis possesses a remarkable abundance of putative surface proteins, which may permit it to be a primary colonizer of the oral cavity and agent of streptococcal endocarditis and infection in neutropenic patients. PMID:17277061
Functional Variation of the Antigen I/II Surface Protein in Streptococcus mutans and Streptococcus intermedius
Petersen, F. C.; Assev, S.; van der Mei, H. C.; Busscher, H. J.; Scheie, A. A.
Although Streptococcus intermedius and Streptococcus mutans are regarded as members of the commensal microflora of the body, S. intermedius is often associated with deep-seated purulent infections, whereas S. mutans is frequently associated with dental caries. In this study, we investigated the roles of the S. mutans and S. intermedius antigen I/II proteins in adhesion and modulation of cell surface characteristics. By using isogenic mutants, we show that the antigen I/II in S. mutans, but not in S. intermedius, was involved in adhesion to a salivary film under flowing conditions, as well as in binding to rat collagen type I. Binding to human fibronectin was a common function associated with the S. mutans and S. intermedius antigen I/II. Adhesion of S. mutans or S. intermedius to human collagen types I or IV was negligible. Hydrophobicity, as measured by water contact angles, and zeta potentials were unaltered in the S. intermedius mutant. The S. mutans isogenic mutants, on the other hand, exhibited more positive zeta potentials at physiological pH values than did the wild type. The results indicate common and species-specific roles for the antigen I/II in mediating the attachment of S. mutans and S. intermedius to host components and in determining cell surface properties. PMID:11748190
Nationwide surveillance of bacterial respiratory pathogens conducted by the Surveillance Committee of Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Clinical Microbiology in 2009: general view of the pathogens' antibacterial susceptibility.
Watanabe, Akira; Yanagihara, Katsunori; Matsumoto, Tetsuya; Kohno, Shigeru; Aoki, Nobuki; Oguri, Toyoko; Sato, Junko; Muratani, Tetsuro; Yagisawa, Morimasa; Ogasawara, Kazuhiko; Koashi, Naoto; Kozuki, Tsuneo; Komoto, Akira; Takahashi, Yoshisaburo; Tsuji, Toshikatsu; Terada, Michinori; Nakanishi, Kunio; Hattori, Rikizo; Hirako, Yukio; Maruo, Akinori; Minamitani, Shinichi; Morita, Kohei; Wakamura, Tomotaro; Sunakawa, Keisuke; Hanaki, Hideaki; Ohsaki, Yoshinobu; Honda, Yasuhito; Sasaoka, Shoichi; Takeda, Hiroaki; Ikeda, Hideki; Sugai, Atsuko; Miki, Makoto; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Kobayashi, Nobuyuki; Takasaki, Jin; Konosaki, Hisami; Aoki, Yasuko; Shoji, Michi; Goto, Hajime; Saraya, Takeshi; Kurai, Daisuke; Okazaki, Mitsuhiro; Kobayashi, Yoshio; Katono, Yasuhiro; Kawana, Akihiko; Saionji, Katsu; Miyazawa, Naoki; Sato, Yoshimi; Watanuki, Yuji; Kudo, Makoto; Ehara, Shigeru; Tsukada, Hiroki; Imai, Yumiko; Watabe, Nobuei; Aso, Sakura; Honma, Yasuo; Mikamo, Hiroshige; Yamagishi, Yuka; Takesue, Yoshio; Wada, Yasunao; Nakamura, Tadahiro; Mitsuno, Noriko; Mikasa, Keiichi; Kasahara, Kei; Uno, Kenji; Sano, Reiko; Miyashita, Naoyuki; Kurokawa, Yukinori; Takaya, Mariko; Kuwabara, Masao; Watanabe, Yaeko; Doi, Masao; Shimizu, Satomi; Negayama, Kiyoshi; Kadota, Junichi; Hiramatsu, Kazufumi; Morinaga, Yoshitomo; Honda, Junichi; Fujita, Masaki; Iwata, Satoshi; Iwamoto, Aikichi; Ezaki, Takayuki; Onodera, Shoichi; Kusachi, Shinya; Tateda, Kazuhiro; Tanaka, Michio; Totsuka, Kyoichi; Niki, Yoshihito; Matsumoto, Tetsuro
For the purpose of nationwide surveillance of antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, the Japanese Society of Chemotherapy (JSC) started a survey in 2006. From 2009, JSC continued the survey in collaboration with the Japanese Association for Infectious Diseases and the Japanese Society for Clinical Microbiology. The fourth-year survey was conducted during the period from January and April 2009 by the three societies. A total of 684 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 635 strains (130 Staphylococcus aureus, 127 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 123 Haemophilus influenzae, 70 Moraxella catarrhalis, 78 Klebsiella pneumoniae, and 103 Pseudomonas aeruginosa). A maximum of 45 antibacterial agents including 26 ?-lactams (four penicillins, three penicillins in combination with ?-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), four aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). Incidence of methicillin-resistant S. aureus (MRSA) was as high as 58.5 %, and that of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) was 6.3 % and 0.0 %, respectively. Among H. influenzae, 21.1 % of them were found to be ?-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 18.7 % to be ?-lactamase-non-producing ABPC-resistant (BLNAR), and 5.7 % to be ?-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5 %) of ?-lactamase-producing strains has been suspected in Moraxella catarrhalis isolates. Four (3.2 %) extended-spectrum ?-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5 %) of P. aeruginosa were found to be metallo-?-lactamase-producing strains, including three (1.9 %) suspected multi-drug resistant strains showing resistance against imipenem, amikacin, and ciprofloxacin. Continuous national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis. PMID:22766652
Streptococcus gordonii septic arthritis : two cases and review of literature
Background Despite advances in antimicrobial and surgical therapy, septic arthritis remains a rheumatologic emergency that can lead to rapid joint destruction and irreversible loss of function. In adults, Staphylococcus aureus is the most common microorganism isolated from native joints. Streptococcus gordonii is a prominent member of the viridans group of oral bacteria and is among the bacteria most frequently identified as being primary agent of subacute bacterial endocarditis. To the best of our knowledge, Streptococcus gordonii has not yet been described as agent of septic arthritis. Case Presentation We describe here two cases of septic arthritis due to Streptococcus gordonii. It gives us an opportunity to review epidemiology, diagnosis criteria and management of septic arthritis. Conclusion Although implication of S. gordonii as aetiologic agent of subacute endocarditis is well known, this organism is a rare cause of septic arthritis. In this case, the exclusion of associated endocarditis is warranted. PMID:22974507
Genome-wide essential gene identification in Streptococcus sanguinis
Xu, Ping; Ge, Xiuchun; Chen, Lei; Wang, Xiaojing; Dou, Yuetan; Xu, Jerry Z.; Patel, Jenishkumar R.; Stone, Victoria; Trinh, My; Evans, Karra; Kitten, Todd; Bonchev, Danail; Buck, Gregory A.
A clear perception of gene essentiality in bacterial pathogens is pivotal for identifying drug targets to combat emergence of new pathogens and antibiotic-resistant bacteria, for synthetic biology, and for understanding the origins of life. We have constructed a comprehensive set of deletion mutants and systematically identified a clearly defined set of essential genes for Streptococcus sanguinis. Our results were confirmed by growing S. sanguinis in minimal medium and by double-knockout of paralogous or isozyme genes. Careful examination revealed that these essential genes were associated with only three basic categories of biological functions: maintenance of the cell envelope, energy production, and processing of genetic information. Our finding was subsequently validated in two other pathogenic streptococcal species, Streptococcus pneumoniae and Streptococcus mutans and in two other gram-positive pathogens, Bacillus subtilis and Staphylococcus aureus. Our analysis has thus led to a simplified model that permits reliable prediction of gene essentiality. PMID:22355642
A graphene/zinc oxide nanocomposite film protects dental implant surfaces against cariogenic Streptococcus mutans.
Kulshrestha, Shatavari; Khan, Shakir; Meena, Ramovatar; Singh, Braj R; Khan, Asad U
Oral biofilms play a crucial role in the development of dental caries and other periodontal diseases. Streptococcus mutans is one of the primary etiological agents in dental caries. Implant systems are regularly employed to replace missing teeth. Oral biofilms accumulate on these implants and are the chief cause of dental implant failure. In the present study, the potential of graphene/zinc oxide nanocomposite (GZNC) against the cariogenic properties of Streptococcus mutans was explored and the anti-biofilm behaviour of artificial acrylic teeth surfaces coated with GZNC was examined. Acrylic teeth are a good choice for implants as they are low cost, have low density and can resist fracture. Microscopic studies and anti-biofilm assays showed a significant reduction in biofilm in the presence GZNC. GZNC was also found to be nontoxic against HEK-293 (human embryonic kidney cell line). The results indicate the potential of GZNC as an effective coating agent for dental implants by efficiently inhibiting S. mutans biofilms. PMID:25431994
The usefulness of biotyping in the determination of selected pathogenicity determinants in Streptococcus mutans
Background Streptococcus mutans is known to be a primary etiological factor of dental caries, a widespread and growing disease in Polish children. Recognition of novel features determining the pathogenicity of this pathogen may contribute to understanding the mechanisms of bacterial infections. The goal of the study was to determine the activity of prephenate dehydrogenase (PHD) and to illuminate the role of the enzyme in S. mutans pathogenicity. The strains were biotyped based on STREPTOtest 24 biochemical identification tests and the usefulness of biotyping in the determination of S. mutans pathogenicity determinants was examined. Results Out of ninety strains isolated from children with deciduous teeth fifty three were classified as S. mutans species. PDH activity was higher (21.69 U/mg on average) in the experimental group compared to the control group (5.74 U/mg on average) (P <0.001). Moreover, it was demonstrated that biotype I, established basing on the biochemical characterization of the strain, was predominant (58.5%) in oral cavity streptococcosis. Its dominance was determined by higher PDH activity compared to biotypes II and III (P?=?0.0019). Conclusions The usefulness of biotyping in the determination of Streptococcus mutans pathogenicity determinants was demonstrated. The obtained results allow for better differentiation of S. mutans species and thus may contribute to recognition of pathogenic bacteria transmission mechanisms and facilitate treatment. PMID:25096795
Effects of simulated microgravity on Streptococcus mutans physiology and biofilm structure.
Cheng, Xingqun; Xu, Xin; Chen, Jing; Zhou, Xuedong; Cheng, Lei; Li, Mingyun; Li, Jiyao; Wang, Renke; Jia, Wenxiang; Li, Yu-Qing
Long-term spaceflights will eventually become an inevitable occurrence. Previous studies have indicated that oral infectious diseases, including dental caries, were more prevalent in astronauts due to the effect of microgravity. However, the impact of the space environment, especially the microgravity environment, on the virulence factors of Streptococcus mutans, a major caries-associated bacterium, is yet to be explored. In the present study, we investigated the impact of simulated microgravity on the physiology and biofilm structure of S. mutans. We also explored the dual-species interaction between S. mutans and Streptococcus sanguinis under a simulated microgravity condition. Results indicated that the simulated microgravity condition can enhance the acid tolerance ability, modify the biofilm architecture and extracellular polysaccharide distribution of S. mutans, and increase the proportion of S. mutans within a dual-species biofilm, probably through the regulation of various gene expressions. We hypothesize that the enhanced competitiveness of S. mutans under simulated microgravity may cause a multispecies micro-ecological imbalance, which would result in the initiation of dental caries. Our current findings are consistent with previous studies, which revealed a higher astronaut-associated incidence of caries. Further research is required to explore the detailed mechanisms. PMID:25109245
The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
Tazi, Asmaa; Disson, Olivier; Bellais, Samuel; Bouaboud, Abdelouhab; Dmytruk, Nicolas; Dramsi, Shaynoor; Mistou, Michel-Yves; Khun, Huot; Mechler, Charlotte; Tardieux, Isabelle; Trieu-Cuot, Patrick
Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17–specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood–brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies. PMID:20956545
Recognition of Streptococcus pneumoniae and Muramyl Dipeptide by NOD2 Results in Potent Induction of MMP-9, Which Can Be Controlled by Lipopolysaccharide Stimulation
Vissers, Marloes; Hartman, Yvonne; Groh, Laszlo; de Jong, Dirk J.; de Jonge, Marien I.
Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis. PMID:25183734
Septic arthritis of the acromioclavicular joint
A. Blankstein; J. L. Amsallem; E. Rubinstein; H. Horoszowski; I. Farin
A patient with isolated pyogenous arthritis of the acromioclavicular joint (A-C joint) caused by Streptococcus viridans is described. The patient had no underlying disease. Minor trauma preceded shortly the development of the septic process. The patient was treated successfully with surgical drainage and antibiotics. To our knowledge this is the first case report of septic arthritis of the A-C joint
Streptococcus oligofermentans Inhibits Streptococcus mutans in Biofilms at Both Neutral pH and Cariogenic Conditions
Bao, Xudong; de Soet, Johannes Jacob; Tong, Huichun; Gao, Xuejun; He, Libang; van Loveren, Cor; Deng, Dong Mei
Homeostasis of oral microbiota can be maintained through microbial interactions. Previous studies showed that Streptococcus oligofermentans, a non-mutans streptococci frequently isolated from caries-free subjects, inhibited the cariogenic Streptococcus mutans by the production of hydrogen peroxide (HP). Since pH is a critical factor in caries formation, we aimed to study the influence of pH on the competition between S. oligofermentans and S. mutans in biofilms. To this end, S. mutans and S. oligofermentans were inoculated alone or mixed at 1:1 ratio in buffered biofilm medium in a 96-well active attachment model. The single- and dual-species biofilms were grown under either constantly neutral pH or pH-cycling conditions. The latter includes two cycles of 8 h neutral pH and 16 h pH 5.5, used to mimic cariogenic condition. The 48 h biofilms were analysed for the viable cell counts, lactate and HP production. The last two measurements were carried out after incubating the 48 h biofilms in buffers supplemented with 1% glucose (pH 7.0) for 4 h. The results showed that S. oligofermentans inhibited the growth of S. mutans in dual-species biofilms under both tested pH conditions. The lactic acid production of dual-species biofilms was significantly lower than that of single-species S. mutans biofilms. Moreover, dual-species and single-species S. oligofermentans biofilms grown under pH-cycling conditions (with a 16 h low pH period) produced a significantly higher amount of HP than those grown under constantly neutral pH. In conclusion, S. oligofermentans inhibited S. mutans in biofilms not only under neutral pH, but also under pH-cycling conditions, likely through HP production. S. oligofermentans may be a compelling probiotic candidate against caries. PMID:26114758
Streptococcus gordonii Hsa Environmentally Constrains Competitive Binding by Streptococcus sanguinis to Saliva-Coated Hydroxyapatite?
Nobbs, Angela H.; Zhang, Yongshu; Khammanivong, Ali; Herzberg, Mark C.
Competition between pioneer colonizing bacteria may determine polymicrobial succession during dental plaque development, but the ecological constraints are poorly understood. For example, more Streptococcus sanguinis than Streptococcus gordonii organisms are consistently isolated from the same intraoral sites, yet S. gordonii fails to be excluded and survives as a species over time. To explain this observation, we hypothesized that S. gordonii could compete with S. sanguinis to adhere to saliva-coated hydroxyapatite (sHA), an in vitro model of the tooth surface. Both species bound similarly to sHA, yet 10- to 50-fold excess S. gordonii DL1 reduced binding of S. sanguinis SK36 by 85 to >95%. S. sanguinis, by contrast, did not significantly compete with S. gordonii to adhere. S. gordonii competed with S. sanguinis more effectively than other species of oral streptococci and depended upon the salivary film on HA. Next, putative S. gordonii adhesins were analyzed for contributions to interspecies competitive binding. Like wild-type S. gordonii, isogenic mutants with mutations in antigen I/II polypeptides (sspAB), amylase-binding proteins (abpAB), and Csh adhesins (cshAB) competed effectively against S. sanguinis. By contrast, an hsa-deficient mutant of S. gordonii showed significantly reduced binding and competitive capabilities, while these properties were restored in an hsa-complemented strain. Thus, Hsa confers a selective advantage to S. gordonii over S. sanguinis in competitive binding to sHA. Hsa expression may, therefore, serve as an environmental constraint against S. sanguinis, enabling S. gordonii to persist within the oral cavity, despite the greater natural prevalence of S. sanguinis in plaque and saliva. PMID:17277052
Differential expression profiles of Streptococcus mutans ftf, gtf and vicR genes in the presence of dietary carbohydrates at early and late exponential growth phases
Moshe Shemesh; Avshalom Tam; Mark Feldman; Doron Steinberg
Dental caries is one of the most common infectious diseases that affects humans. Streptococcus mutans, the main pathogenic bacterium associated with dental caries, produces a number of extracellular sucrose-metabolizing enzymes, such as glucosyltransferases (GTFB, GTFC and GTFD) and fructosyltransferase (FTF). The cooperative action of these enzymes is essential for sucrose-dependent cellular adhesion and biofilm formation. A global response regulator (vicR)
Use of in vivo-induced antigen technology (IVIAT) for the identification of Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens
Hongwei Gu; Haodan Zhu; Chengping Lu
BACKGROUND: Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes death and disease in both humans and swine. A better understanding of SS2-host molecular interactions is crucial for understanding SS2 pathogenesis and immunology. Conventional genetic and biochemical approaches used to study SS2 virulence factors are unable to take into account the complex and dynamic environmental stimuli associated with
Outbreak of Streptococcus equi subsp. zooepidemicus infections on the island of Gran Canaria associated with the consumption of inadequately pasteurized cheese
A. Bordes-Benítez; M. Sánchez-Ońoro; P. Suárez-Bordón; A. J. García-Rojas; J. A. Saéz-Nieto; A. González-García; I. Álamo-Antúnez; A. Sánchez-Maroto; M. Bolańos-Rivero
Streptococcus equi subsp. zooepidemicus infections are infrequent in humans. A clinical and epidemiological study of a milk-borne outbreak caused by this organism is described. Fifteen patients (5 females, 10 males) with a median age of 70 years (range 47–86) were infected. Twelve (80%) had underlying diseases. Infection with S. equi subsp. zooepidemicus presented as primary bacteremia in six cases, as bacteremia
Development of a Rapid PCR Assay for Screening of Maternal Colonization by Group B Streptococcus and Neonatal Invasive Escherichia coli during Labor
Begońa Martínez de Tejada; Catalin M. Stan; Michel Boulvain; Gesuele Renzi; Patrice François; Olivier Irion; Jacques Schrenzel
Objective: Group B Streptococcus (GBS) and Escherichiacoli(E. coli) are the leading causes of early-onset neonatal disease (EOD). Intrapartum antibiotic prophylaxis of GBS-colonized women decreases vertical transmission and EOD due to GBS. Nevertheless, no intervention has been developed to reduce the risk of EOD related to E. coli. Timely and accurate identification of colonized mothers is necessary to implement preventive strategies
Efficacy profiles of daptomycin for treatment of invasive and noninvasive pulmonary infections with Streptococcus pneumoniae.
Henken, Stefanie; Bohling, Jennifer; Martens-Lobenhoffer, Jens; Paton, James C; Ogunniyi, A David; Briles, David E; Salisbury, Vyvyan C; Wedekind, Dirk; Bode-Böger, Stefanie M; Welsh, Thomas; Bange, Franz C; Welte, Tobias; Maus, Ulrich A
Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to approximately 70% or approximately 60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease. PMID:19917756
Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with Streptococcus pneumoniae?
Henken, Stefanie; Bohling, Jennifer; Martens-Lobenhoffer, Jens; Paton, James C.; Ogunniyi, A. David; Briles, David E.; Salisbury, Vyvyan C.; Wedekind, Dirk; Bode-Böger, Stefanie M.; Welsh, Thomas; Bange, Franz C.; Welte, Tobias; Maus, Ulrich A.
Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ?70% or ?60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease. PMID:19917756
Streptococcus: A World-Wide Fish Health Problem
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus iniae and S. agalactiae are important emergent-epizootic pathogens which affect many fish species world-wide, especially in warm-water regions. Further, these Gram-positive bacteria cause significant economic losses in marine and freshwater aquaculture systems with an estimated loss i...
Streptococcus troglodytae sp. nov., from the chimpanzee oral cavity.
Okamoto, Masaaki; Imai, Susumu; Miyanohara, Mayu; Saito, Wataru; Momoi, Yasuko; Abo, Tomoko; Nomura, Yoshiaki; Ikawa, Tomoko; Ogawa, Takumi; Miyabe-Nishiwaki, Takako; Kaneko, Akihisa; Watanabe, Akino; Watanabe, Shohei; Hayashi, Misato; Tomonaga, Masaki; Hanada, Nobuhiro
Six strains, TKU 25, TKU 28, TKU 30, TKU 31(T), TKU 33 and TKU 34, were isolated from the oral cavity of a chimpanzee (Pan troglodytes). Colonies of strains grown on Mitis-Salivarius agar were similar in morphology to that of Streptococcus mutans. The novel strains were Gram-stain-positive, facultatively anaerobic cocci that lacked catalase activity. Analysis of the partial 16S rRNA gene sequences of these isolates showed that the most closely related strain was the type strain of S. mutans (96.4?%). The next closely related strains to the isolates were the type strains of Streptococcus devriesei (94.5?%) and Streptococcus downei (93.9?%). These isolates could be distinguished from S. mutans by inulin fermentation and alkaline phosphatase activity (API ZYM system). The peptidoglycan type of the novel isolates was Glu-Lys-Ala(3). Strains were not susceptible to bacitracin. On the basis of phenotypic characterization, partial 16S rRNA gene and two housekeeping gene (groEL and sodA) sequence data, we propose a novel taxon, Streptococcus troglodytae sp. nov.; the type strain is TKU 31(T) (?=?JCM 18038(T)?=?DSM 25324(T)). PMID:22447699
Potential virulence factors of Streptococcus dysgalactiae associated with bovine mastitis
L. F Calvinho; R. A Almeida; S. P Oliver
Mastitis caused by environmental pathogens is a major problem that affects many well-managed dairy herds. Among the environmental pathogens, Streptococcus dysgalactiae is isolated frequently from intramammary infections during lactation and during the nonlactating period. In spite of its high prevalence, little is known about factors that contribute to the virulence of S. dysgalactiae. During the last decade, several cell-associated and
Biofilm Production by Streptococcus uberis Associated with Intramammary Infections
Glenis Elizabeth Moore
Abstract Mastitis is the inflammation,of the mammary,gland and is extremely problematic in the dairy industry, annually costing upwards of two billion dollars. Streptococcus uberisis one of the main infectious agents responsible for causing mastitis. We speculate that one of the reasons behind the prevalence of S. uberisinfections is its ability to form biofilms. The objectives of this study were to
Ubericin A, a Class IIa Bacteriocin Produced by Streptococcus uberis? †
Heng, Nicholas C. K.; Burtenshaw, Grace A.; Jack, Ralph W.; Tagg, John R.
Streptococcus uberis, a causal agent of bovine mastitis, produces ubericin A, a 5.3-kDa class IIa (pediocin-like) bacteriocin, which was purified and characterized. The uba locus comprises two overlapping genes: ubaA (ubericin A precursor peptide) and ubaI (putative immunity protein). Ubericin A is the first streptococcal class IIa bacteriocin to be characterized. PMID:17933926
Monoclonal antibody recognizing a species-specific protein from Streptococcus pneumoniae.
Russell, H; Tharpe, J A; Wells, D E; White, E H; Johnson, J E
Monoclonal antibodies (MAbs) against a nonencapsulated strain (R36A) of Streptococcus pneumoniae were produced to aid in a search for antigens common to this species. By Western immunoblot analysis, a species-specific 37-kilodalton (kDa) protein was found in lysates of 24 different encapsulated strains of S. pneumoniae. Monoclonal antibodies against the 37-kDa antigen did not react with 55 heterologous strains representing 19 genera and 36 species of bacteria that can also cause acute lower respiratory tract disease. Immunogold staining suggests that the antigen is synthesized inside the pneumococcal cell. However, MAbs to the 37-kDa antigen bound whole cells in the enzyme-linked immunosorbent assay and the indirect immunofluorescence assay. Antibody-binding epitopes of the antigen are probably exposed on the outer surface of the pneumococcus cell wall. The effectiveness of the 37-kDa antigen as a useful diagnostic marker is under study. Images PMID:2229341
Streptococcus pneumoniae damages the ciliated ependyma of the brain during meningitis.
Hirst, Robert A; Gosai, Bejal; Rutman, Andrew; Andrew, Peter W; O'Callaghan, Christopher
Streptococcus pneumoniae meningitis remains a disease with a poor outcome for the patient. A region of the brain that has been neglected in the study of meningitis is the ependyma, which has been identified as a location of adult pluripotent cells. In this study we have used a rat model of meningitis to examine whether the ependymal layer is affected by S. pneumoniae. The effects included localized loss of cilia, a decrease of the overall ependymal ciliary beat frequency, and damage to the ependymal ultrastructure during meningitis. In conclusion, loss of ependymal cells and ciliary function exposes the underlying neuronal milieu to host and bacterial cytotoxins and this is likely to contribute to the neuropathology commonly observed in pneumococcal meningitis. PMID:14500537
Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae
Watkins, Eleanor R.; Penman, Bridget S.; Lourenço, José; Buckee, Caroline O.; Maiden, Martin C. J.; Gupta, Sunetra
The bacterial pathogen, Streptococcus pneumoniae (the pneumococcus), is a leading cause of life-threatening illness and death worldwide. Available conjugate vaccines target only a small subset (up to 13) of >90 known capsular serotypes of S. pneumoniae and, since their introduction, increases in non-vaccine serotypes have been recorded in several countries: a phenomenon termed Vaccine Induced Serotype Replacement (VISR). Here, using a combination of mathematical modelling and whole genome analysis, we show that targeting particular serotypes through vaccination can also cause their metabolic and virulence-associated components to transfer through recombination to non-vaccine serotypes: a phenomenon we term Vaccine-Induced Metabolic Shift (VIMS). Our results provide a novel explanation for changes observed in the population structure of the pneumococcus following vaccination, and have important implications for strain-targeted vaccination in a range of infectious disease systems. PMID:26181911
Endocarditis with Ruptured Sinus of Valsalva Aneurysm Caused by Nonvaccine Streptococcus pneumoniae Serotype 21
Patra, Kamakshya P.; Vanchiere, John A.; Bocchini, Joseph A.; Wu, Amy C.; Jackson, Robert D.; Kiel, Ernest A.; Mello, Dennis
Sinus of Valsalva aneurysm is a rare, catastrophic complication of endocarditis. We report an unusual case of ruptured sinus of Valsalva aneurysm associated with endocarditis that was caused by Streptococcus pneumoniae serotype 21. The patient, a 12-year-old girl, underwent surgical repair of the aneurysm and was given intravenous antibiotics for 6 weeks. She was doing well at the 6-week follow-up visit. This case is unusual because of the patient's young age at presentation, the absence of predisposing factors, and the isolation of a nonvaccine serotype 21, which revealed the epidemiologic changes of invasive pneumococcal disease. To our knowledge, this is the first reported case of endocarditis caused by this S. pneumoniae serotype. PMID:22740753
PCR based differentiation between Streptococcus dysgalactiae subsp. equisimilis strains isolated from humans and horses.
Preziuso, S; Pinho, M D; Attili, A R; Melo-Cristino, J; Acke, E; Midwinter, A C; Cuteri, V; Ramirez, M
Streptococcus dysgalactiae subsp. equisimilis (SDSE) can be severely pathogenic in humans and is increasingly isolated from horses with respiratory, reproductive or other diseases, although it is often considered a commensal bacterium. Here a PCR protocol is described for identifying SDSE recovered from humans. A multiplex PCR targeting the 16S rRNA and the streptokinase precursor gene has been optimized for differentiating between SDSE strains isolated from humans and those isolated from horses. Previously, the sequence of the streptokinase precursor gene of SDSE recovered from horses has been found in two human cases of pneumonia in Japan. Although further evaluation is required, the findings of this study suggest that SDSE strains are host-specific and this multiplex PCR protocol can be useful in further epidemiological studies and for investigating the zoonotic potential of SDSE. PMID:24813401
The Antimicrobial Effect of Silver Ion Impregnation into Endodontic Sealer against Streptococcus mutans
Kreth, J.; Kim, D.; Nguyen, M.; Hsiao, G.; Mito, R.; Kang, M.K.; Chugal, N.; Shi, W.
Pulpal and periradicular diseases are primarily caused by bacterial invasion of the root canal system as a result of caries progression. The presence of residual bacteria at the time of root canal completion (obturation) is associated with significantly higher rate of treatment failure. Re-infection of obturated root canals can be potentially prevented by enhancing the antibacterial activities of root canal obturation materials. We evaluated, in an in vitro model, the antimicrobial efficacy of silver ions added to a common endodontic sealer. For that purpose we performed growth inhibition studies and bacterial viability tests. We measured the zone of inhibition, optical density and performed confocal laser scanning microscopy. Our results show that the silver ions enhance the antimicrobial activity of the root canal sealer against Streptococcus mutans. This study approach may hold promise for studying other biologically based therapies and therefore increasing the success rate of routine orthograde root canal treatment. PMID:19088878
Deriving Group A Streptococcus Typing Information from Short-Read Whole-Genome Sequencing Data
Athey, Taryn B. T.; Teatero, Sarah; Li, Aimin; Marchand-Austin, Alex; Beall, Bernard W.
Typing of group A Streptococcus (GAS) is crucial for infection control and epidemiology. While whole-genome sequencing (WGS) is revolutionizing the way that bacterial organisms are typed, it is necessary to provide backward compatibility with currently used typing schemas to facilitate comparisons and understanding of epidemiological trends. Here, we sequenced the genomes of 191 GAS isolates representing 42 different emm types and used bioinformatics tools to derive commonly used GAS typing information directly from the short-read WGS data. We show that emm typing and multilocus sequence typing can be achieved rapidly and efficiently using this approach, which also permits the determination of the presence or absence of genes associated with GAS tissue tropism. We also report on how the WGS data analysis was instrumental in identifying ambiguities present in the commonly used emm type database hosted by the U.S. Centers for Disease Control and Prevention. PMID:24648555
Strategies for the control of pneumococcal diseases
Kim Mulholland
Streptococcus pneumoniae (pneumococcus) is a Gram-positive, encapsulated bacteria that is a major cause of human disease in people of all ages. It is the most important cause of bacterial pneumonia in infancy, childhood and adult life, and the most important cause of meningitis in all age groups except children of 3 months to 2 years in whom Haemophilus influenzae type
Haemorrhagic pneumonia in sled dogs caused by Streptococcus equi subsp. zooepidemicus - one fatality and two full recoveries: a case report
In spite of yearly vaccination, outbreaks of canine infectious respiratory disease are periodically seen amongst domestic dogs. These infections compromise host defense mechanisms, and, when combined with other stressful events, allow opportunistic pathogens like Streptococcus equi subsp. zooepidemicus to create serious disease. Early recognition and treatment are tremendously important for a successful outcome in these cases. A polyvalent vaccine was given to 22 racing dogs three days after a competition, followed by two days of rest, and then the dogs were returned to regular training. Coughing was noticed among the dogs four days after immunisation. Three days after this outbreak one of the dogs was unusually silent and was found dead the next morning. Simultaneously two other dogs developed haemorrhagic expectorate, depression and dyspnea and were brought in to the veterinary hospital. Streptococcus equi subsp. zooepidemicus was isolated in pure culture from all three cases. They were treated and rehabilitated successfully, and won a sledge race three months later. This paper discusses the necropsy results, treatment regime, rehabilitation and the chronology of vaccination, stressful events and disease. PMID:24020788
Safety and Effectiveness of Long-Term Interferon Gamma Therapy in Patients with Chronic Granulomatous Disease
Lynn S. Bemiller; David H. Roberts; Karen M. Starko; John T. Curnutte
In chronic granulomatous disease (CGD), diminished or absent neutrophil NADPH oxidase function leads to recurrent pyogenic infections and granuloma formation. In a recent randomized, placebo-controlled trial, short-term prophylactic use of recombinant human interferon gamma (rIFN-? 1b) reduced the risk of serious infection in CGD patients by 67%. The current study evaluated the safety and effectiveness of long-term rIFN-? therapy in
Epstein-barr Virus Associated Extranodal Natural Killer T Cell Lymphoma of Nasal Type Mimicking Pyogenic Osteomyelitis of the Proximal Humerus
To Wong; Jih-Yang Ko; Feng-Sheung Wang; Yi-Ju Chen; Ming-Chun Ma
Extranodal natural killer (NK) cell lymphoma\\/leukemia, nasal type, is rare but highly aggressive. These neoplasms are found to be associated with infection of the Epstein-barr virus (EBV). We report a male patient who suffered from EBV associated NK\\/T cell lym- phoma of the proximal humerus but presented as pyogenic osteomyelitis with the clinical signs and symptoms of fever, local erythema,
The gene encoding pyolysin, the pore-forming toxin of Arcanobacterium pyogenes, resides within a genomic islet flanked by essential genes
Stefani T. Rudnick; B. Helen Jost; J. Glenn Songer; Stephen J. Billington
The plo gene, encoding the Arcanobacterium pyogenes cholesterol-dependent cytolysin, pyolysin (PLO), was localized to a 2.7-kb genomic islet of reduced %G+C content and alternate codon usage frequency. This islet, conserved among isolates from diverse hosts and geographical locations, separated the housekeeping genes smc and ftsY, which are found adjacent in many prokaryotes. The ftsY and ffh genes, located downstream of
Acne as a chronic systemic disease.
Zouboulis, Christos C
Acne is the most common skin disorder. In the majority of cases, acne is a disease that changes its skin distribution and severity over time; moreover, it can be a physically (scar development) and psychologically damaging condition that lasts for years. According to its clinical characteristics, it can be defined as a chronic disease according to the World Health Organization criteria. Acne is also a cardinal component of many systemic diseases or syndromes, such as congenital adrenal hyperplasia, seborrhea-acne-hirsutism-androgenetic alopecia syndrome, polycystic ovarian syndrome, hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, Apert syndrome, synovitis-acne-pustulosis-hyperostosis-osteitis syndrome, and pyogenic arthritis-pyoderma gangrenosum-acne syndrome. Recent studies on the Ache hunter gatherers of Paraguay detected the lack of acne in association with markedly lower rates of obesity, diabetes mellitus, hyperlipidemia, and cardiovascular diseases, a finding that indicates either a nutritional or a genetic background of this impressive concomitance. PMID:24767186
Darier disease: A fold (intertriginous) dermatosis.
Engin, Burhan; Kutlubay, Zekayi; Erkan, Emine; Tüzün, Yalç?n
Darier disease, also known as Darier-White disease, is characterized by yellow to brown, oily keratotic papules and plaques in the seborrheic areas of the face and chest. This disorder may show different clinical manifestations, such as palmoplantar pits and nail abnormalities. The trigger factors are mechanical trauma, heat, humidity, ultraviolet B, and pyogenic infections. The disease usually becomes apparent in the second decade of life. The ATP2 A2 (SERCA2) gene mutation was detected in all patients. Histopathologic changes include epidermal adhesion loss, acantholysis, abnormal keratinization, eosinophilic dyskeratotic cells in the spinous layer known as corps ronds, and the presence of grains in the stratum corneum. Although the treatment for Darier disease is unsatisfactory, some relief has been achieved with the use of corticosteroids and retinoids. PMID:26051059
Glucose uptake by Streptococcus mutans, Streptococcus mitis, and Actinomyces viscosus in the presence of human saliva.
Germaine, G R; Tellefson, L M
Glucose uptake was examined by using whole-cell suspensions of Streptococcus mutans (strains BHT, Ingbritt, and GS-5), Streptococcus mitis (strains 9811 and 72x41), and Actinomyces viscosus (strains T6 and WVU626) incubated for up to 90 min in 0 to 82% (vol/vol) human whole salivary supernatant. Glucose uptake by the S. mutans strains was completely inhibited at all saliva concentrations. Dithiothreitol (DTT), present during saliva incubation, prevented saliva inhibition. Glucose uptake was also restored when saliva-inhibited cells were subsequently exposed to DTT. The inclusion of catalase in the saliva incubation mixtures resulted in protection equal to that obtained with DTT. The S. mitis strains were also inhibited by saliva but to a far lesser extent that S. mutans. DTT and catalase also protected S. mitis from saliva inhibition. Both A. viscosus strains were completely refractory to saliva inhibition of glucose uptake. Based on (i) the sensitivity of the catalase-negative streptococci and the resistance of catalase-positive actinomyces to saliva inhibition and (ii) the equal and complete protection to saliva inhibition afforded by DTT and catalase, we conclude that the lactoperoxidase-SCN(-)-H(2)O(2) system in saliva was the only antibacterial system expressed under our experimental conditions. The relative resistance of S. mitis 9811 (compared with S. mutans BHT) to saliva inhibition was shown not to result from poor H(2)O(2) production in either glucose-supplemented buffer or saliva solutions. S. mitis produced inhibitory quantities of H(2)O(2) that equaled or exceeded S. mutans H(2)O(2) accumulation. It is suggested that S. mitis might possess a greater ability to repair lactoperoxidase-mediated damage than does S. mutans. Every organism studied exhibited a saliva concentration-dependent, cell growth-independent stimulation of glucose uptake after 60 to 90 min of incubation. The A. viscosus and S. mitis strains showed saliva stimulation (or stabilization) of glucose uptake with unsupplemented saliva. In the case of S. mutans, saliva stimulation was only observed when DTT was present. The possible role of salivary lactoperoxidase as a modulator of the intraoral site specificities exhibited by S. mutans is discussed. PMID:7152663
Non-typeable Haemophilus influenzae and Streptococcus pneumoniae as primary causes of acute otitis media in colombian children: a prospective study
Background Acute otitis media (AOM) is one of the most frequently encountered bacterial infections in children aged < 5 years; Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are historically identified as primary AOM causes. Nevertheless, recent data on bacterial pathogens causing AOM in Latin America are limited. This prospective study aimed to identify and characterize bacterial etiology and serotypes of AOM cases including antimicrobial susceptibility in < 5 year old Colombian children. Methods From February 2008 to January 2009, children ?3 months and < 5 years of age presenting with AOM and for whom a middle ear fluid (MEF) sample was available were enrolled in two medical centers in Cali, Colombia. MEF samples were collected either by tympanocentesis procedure or spontaneous otorrhea swab sampling. Bacteria were identified using standard laboratory methods, and antimicrobial resistance testing was performed based on the 2009 Clinical and Laboratory Standards Institute (CLSI) criteria. Most of the cases included in the study were sporadic in nature. Results Of the 106 enrolled children, 99 were included in the analysis. Bacteria were cultured from 62/99 (63%) of samples with S. pneumoniae, H. influenzae, or S. pyogenes. The most commonly isolated bacteria were H. influenzae in 31/99 (31%) and S. pneumoniae in 30/99 (30%) of samples. The majority of H. influenzae episodes were NTHi (27/31; 87%). 19F was the most frequently isolated pneumococcal serotype (10/30; 33%). Of the 30 S. pneumoniae positive samples, 8/30 (27%) were resistant to tetracycline, 5/30 (17%) to erythromycin and 8/30 (27%) had intermediate resistance to penicillin. All H. influenzae isolates tested were negative to beta-lactamase. Conclusions NTHi and S. pneumoniae are the leading causes of AOM in Colombian children. A pneumococcal conjugate vaccine that prevents both pathogens could be useful in maximizing protection against AOM. PMID:21208431
The Streptococcus sanguinis Competence Regulon Is Not Required for Infective Endocarditis Virulence in a Rabbit Model
Jill E. Callahan; Cindy L. Munro; Todd Kitten
Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon
Adherence ofCandida albicansto a Cell Surface Polysaccharide Receptor onStreptococcus gordonii
CandidaalbicansATCC10261andCA2boundtocellsoftheoralbacteriaStreptococcusgordonii,Streptococcus oralis, andStreptococcus sanguiswhen these bacteria were immobilized onto microtiter plate wells, but they did not bind to cells ofStreptococcus mutansorStreptococcus salivarius. Cell wall polysaccharide was extracted with alkali fromS. gordoniiNCTC 7869, the streptococcal species to whichC. albicansbound with highest affinity, andwaseffectiveinblockingthecoaggregationofC.albicansandS.gordoniicellsinthefluidphase.Whenfixed to microtiter plate wells, the S. gordonii polysaccharide was bound by all strains of C. albicans tested. The
Drug-resistant Streptococcus pneumoniae in community-acquired pneumonia
Michael Henry; Howard L. Leaf
The emergence of Streptococcus pneumoniae isolates resistant to not only penicillin, but to other antipneumococcal agents as well, has major public health implications.\\u000a Drug-resistant S. pneumoniae are distributed worldwide, and resistance has become increasingly prevalent in the United States within the past decade.\\u000a The relevance of resistance, particularly to the ?-lactams, to treatment outcome has been subject to debate. Pneumonia
[Dentogenic infection due to Streptococcus constellatus in a child].
Handrick, W; Schille, R; Hemprich, A; Spencker, F B
An 8-year-old boy was admitted with a pain-full swelling at the right mandible and symptoms of septicemia. The illness was caused by a dental infection due to Streptococcus constellatus proved by isolation from blood culture, the origin was a decayed tooth. Treatment comprised suitable antibiotics, extraction of the tooth and local irrigations with chlorhexidine solution. General condition improved rapidly, the local situation rather slowly, however. PMID:11582531
Group A Streptococcus : A Loser in the Battle with Autophagy
Tamotsu Yoshimori; Atsuo Amano
\\u000a Autophagy is an intracellular bulk degradation\\/recycling system for turning over cellular constituents. In one of the more\\u000a remarkable findings among the recent developments in the field of autophagy, it was found that autophagy can also eliminate\\u000a bacteria that invade host cells. The first evidence of this phenomenon came from an analysis of group A Streptococcus (GAS), the etiological agent underlying
Inhibitory Activity by Barley Coffee Components Towards Streptococcus Mutans Biofilm
Monica Stauder; Adele Papetti; Maria Daglia; Luigi Vezzulli; Gabriella Gazzani; Pietro E. Varaldo; Carla Pruzzo
It was shown that barley coffee (BC) interferes with Streptococcus mutans adsorption to hydroxyapatite. After BC component fractionation by dialysis and gel filtration chromatography (GFC), it was\\u000a found that the low molecular mass (<1,000 Da) fraction (LMM fraction) containing polyphenols, zinc and fluoride ions and,\\u000a above all, a high molecular mass (HMM > 1,000 kDa) melanoidin fraction display strong anti-adhesive properties towards S. mutans.
Characterization of salivary alpha-amylase binding to Streptococcus sanguis
Scannapieco, F.A.; Bergey, E.J.; Reddy, M.S.; Levine, M.J. (State Univ. of New York, Buffalo (USA))
The purpose of this study was to identify the major salivary components which interact with oral bacteria and to determine the mechanism(s) responsible for their binding to the bacterial surface. Strains of Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans, and Actinomyces viscosus were incubated for 2 h in freshly collected human submandibular-sublingual saliva (HSMSL) or parotid saliva (HPS), and bound salivary components were eluted with 2% sodium dodecyl sulfate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western transfer, alpha-amylase was the prominent salivary component eluted from S. sanguis. Studies with {sup 125}I-labeled HSMSL or {sup 125}I-labeled HPS also demonstrated a component with an electrophoretic mobility identical to that of alpha-amylase which bound to S. sanguis. Purified alpha-amylase from human parotid saliva was radiolabeled and found to bind to strains of S. sanguis genotypes 1 and 3 and S. mitis genotype 2, but not to strains of other species of oral bacteria. Binding of ({sup 125}I)alpha-amylase to streptococci was saturable, calcium independent, and inhibitable by excess unlabeled alpha-amylases from a variety of sources, but not by secretory immunoglobulin A and the proline-rich glycoprotein from HPS. Reduced and alkylated alpha-amylase lost enzymatic and bacterial binding activities. Binding was inhibited by incubation with maltotriose, maltooligosaccharides, limit dextrins, and starch.
Characterization of salivary alpha-amylase binding to Streptococcus sanguis.
Scannapieco, F A; Bergey, E J; Reddy, M S; Levine, M J
The purpose of this study was to identify the major salivary components which interact with oral bacteria and to determine the mechanism(s) responsible for their binding to the bacterial surface. Strains of Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans, and Actinomyces viscosus were incubated for 2 h in freshly collected human submandibular-sublingual saliva (HSMSL) or parotid saliva (HPS), and bound salivary components were eluted with 2% sodium dodecyl sulfate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western transfer, alpha-amylase (EC 220.127.116.11) was the prominent salivary component eluted from S. sanguis. Studies with 125I-labeled HSMSL or 125I-labeled HPS also demonstrated a component with an electrophoretic mobility identical to that of alpha-amylase which bound to S. sanguis. Purified alpha-amylase from human parotid saliva was radiolabeled and found to bind to strains of S. sanguis genotypes 1 and 3 and S. mitis genotype 2, but not to strains of other species of oral bacteria. Binding of [125I]alpha-amylase to streptococci was saturable, calcium independent, and inhibitable by excess unlabeled alpha-amylases from a variety of sources, but not by secretory immunoglobulin A and the proline-rich glycoprotein from HPS. Reduced and alkylated alpha-amylase lost enzymatic and bacterial binding activities. Binding was inhibited by incubation with maltotriose, maltooligosaccharides, limit dextrins, and starch. Images PMID:2788139
Characterization of salivary alpha-amylase binding to Streptococcus sanguis.
Scannapieco, F A; Bergey, E J; Reddy, M S; Levine, M J
The purpose of this study was to identify the major salivary components which interact with oral bacteria and to determine the mechanism(s) responsible for their binding to the bacterial surface. Strains of Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans, and Actinomyces viscosus were incubated for 2 h in freshly collected human submandibular-sublingual saliva (HSMSL) or parotid saliva (HPS), and bound salivary components were eluted with 2% sodium dodecyl sulfate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western transfer, alpha-amylase (EC 188.8.131.52) was the prominent salivary component eluted from S. sanguis. Studies with 125I-labeled HSMSL or 125I-labeled HPS also demonstrated a component with an electrophoretic mobility identical to that of alpha-amylase which bound to S. sanguis. Purified alpha-amylase from human parotid saliva was radiolabeled and found to bind to strains of S. sanguis genotypes 1 and 3 and S. mitis genotype 2, but not to strains of other species of oral bacteria. Binding of [125I]alpha-amylase to streptococci was saturable, calcium independent, and inhibitable by excess unlabeled alpha-amylases from a variety of sources, but not by secretory immunoglobulin A and the proline-rich glycoprotein from HPS. Reduced and alkylated alpha-amylase lost enzymatic and bacterial binding activities. Binding was inhibited by incubation with maltotriose, maltooligosaccharides, limit dextrins, and starch. PMID:2788139
Streptococcus pneumoniae from Palestinian Nasopharyngeal Carriers: Serotype Distribution and Antimicrobial Resistance
Ramlawi, Asad; Salman, Nisreen; Salem, Ibrahim; Abdeen, Ziad
Infections of Streptococcus pneumoniae in children can be prevented by vaccination; left untreated, they cause high morbidity and fatalities. This study aimed at determining the nasopharyngeal carrier rates, serotype distribution and antimicrobial resistance patterns of S. pneumoniae in healthy Palestinian children under age two prior to the full introduction of the pneumococcal 7-valent conjugate vaccine (PCV7), which was originally introduced into Palestine in a pilot trial in September, 2010. In a cross sectional study, nasopharyngeal specimens were collected from 397 healthy children from different Palestinian districts between the beginning of November 2012 to the end of January 2013. Samples were inoculated into blood agar and suspected colonies were examined by amplifying the pneumococcal-specific autolysin gene using a real-time PCR. Serotypes were identified by a PCR that incorporated different sets of specific primers. Antimicrobial susceptibility was measured by disk diffusion and MIC methods. The resulting carrier rate of Streptococcus pneumoniae was 55.7% (221/397). The main serotypes were PCV7 serotypes 19F (12.2%), 23F (9.0%), 6B (8.6%) and 14 (4%) and PCV13 serotypes 6A (13.6%) and 19A (4.1%). Notably, serotype 6A, not included in the pilot trial (PCV7) vaccine, was the most prevalent. Resistance to more than two drugs was observed for bacteria from 34.1% of the children (72/211) while 22.3% (47/211) carried bacteria were susceptible to all tested antibiotics. All the isolates were sensitive to cefotaxime and vancomycin. Any or all of these might impinge on the type and efficacy of the pneumococcal conjugate vaccines and antibiotics to be used for prevention and treatment of pneumococcal disease in the country. PMID:24339987
Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus
Wolf, Amaya I.; Strauman, Maura C.; Mozdzanowska, Krystyna; Whittle, James R. R.; Williams, Katie L.; Sharpe, Arlene H.; Weiser, Jeffrey N.; Caton, Andrew J.; Hensley, Scott E.
ABSTRACT Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4+ T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. IMPORTANCE Respiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection. PMID:25100838
Tumor Suppressor Cylindromatosis Acts as a Negative Regulator for Streptococcus pneumoniae-induced NFAT Signaling*
Koga, Tomoaki; Lim, Jae Hyang; Jono, Hirofumi; Ha, Un Hwan; Xu, Haidong; Ishinaga, Hajime; Morino, Saori; Xu, Xiangbin; Yan, Chen; Kai, Hirofumi; Li, Jian-Dong
Gram-positive bacterium Streptococcus pneumoniae is an important human pathogen that colonizes the upper respiratory tract and is also the major cause of morbidity and mortality worldwide. S. pneumoniae causes invasive diseases such as pneumonia, meningitis, and otitis media. Despite the importance of pneumococcal diseases, little is known about the molecular mechanisms by which S. pneumoniae-induced inflammation is regulated, especially the negative regulatory mechanisms. Here we show that S. pneumoniae activates nuclear factor of activated T cells (NFAT) signaling pathway and the subsequent up-regulation of inflammatory mediators via a key pneumococcal virulence factor, pneumolysin. We also demonstrate that S. pneumoniae activates NFAT transcription factor independently of Toll-like receptors 2 and 4. Moreover, S. pneumoniae induces NFAT activation via both Ca2+-calcineurin and transforming growth factor-?-activated kinase 1 (TAK1)-mitogen-activated protein kinase kinase (MKK) 3/6-p38?/?-dependent signaling pathways. Interestingly, we found for the first time that tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for S. pneumoniae-induced NFAT signaling pathway via a deubiquitination-dependent mechanism. Finally, we showed that CYLD interacts with and deubiquitinates TAK1 to negatively regulate the activation of the downstream MKK3/6-p38?/? pathway. Our studies thus bring new insights into the molecular pathogenesis of S. pneumoniae infections through the NFAT-dependent mechanism and further identify CYLD as a negative regulator for NFAT signaling, thereby opening up new therapeutic targets for these diseases. PMID:18332137
Emergence of Vancomycin Resistance in the GenusStreptococcus: Characterization of avanBTransferable Determinant inStreptococcus bovis
Streptococcus bovis NEM760 was isolated from a stool swab collected on admission from a patient as surveillance for vancomycin-resistant enterococci. Strain NEM760 was identified as S. bovis by conventional biochemical methods and partial sequence analysis of its 16S rRNA. This strain was resistant to a low level of vancomycin (MIC, 64 mg\\/ml) but was susceptible to teicoplanin (MIC, 1 mg\\/ml),
Bone marrow transplantation for chronic granulomatous disease: long-term follow-up and review of literature
TF Leung; KW Chik; CK Li; MMK Shing; PMP Yuen
Chronic granulomatous disease (CGD) is a heterogeneous group of disorders with defective respiratory burst activity in phagocytes which results in recurrent pyogenic infections. We report an 8-year-old boy with X-linked CGD who received an HLA-identical BMT from his sister. The nitroblue tetrazolium test returned to normal 3 months post transplant. Neutrophil engraftment has been stable for 7 years post BMT.
Ophüls, W.
From the preceding I derive the following conclusions: 1. The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus. 2. The infection may primarily be either a cutaneous or a pulmonary one. 3. The lesions produced by this fungus fall under the general head of infectious granulomata and consist partly in nodules resembling altogether those produced by the tubercle bacilli and partly in chronic abscesses. 4. The adult forms of the parasite are more apt to produce nodules, the sporulating forms abscesses. 5. The fungus is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which we encounter in the human being in this disease. 6. Supurative periorchitis in guinea-pigs is not pathognomonic for glanders. PMID:19866981
A Novel C5a-Derived Immunobiotic Peptide Reduces Streptococcus agalactiae Colonization through Targeted Bacterial Killing
Cavaco, Courtney K.; Patras, Kathryn A.; Zlamal, Jaime E.; Thoman, Marilyn L.; Morgan, Edward L.; Sanderson, Sam D.
Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Current prophylaxis, consisting of late gestation screening and intrapartum antibiotics, has failed to completely prevent transmission, and GBS remains a leading cause of neonatal sepsis and meningitis in the United States. Lack of an effective vaccine and emerging antibiotic resistance necessitate exploring novel therapeutic strategies. We have employed a host-directed immunomodulatory therapy using a novel peptide, known as EP67, derived from the C-terminal region of human complement component C5a. Previously, we have demonstrated in vivo that EP67 engagement of the C5a receptor (CD88) effectively limits staphylococcal infection by promoting cytokine release and neutrophil infiltration. Here, using our established mouse model of GBS vaginal colonization, we observed that EP67 treatment results in rapid clearance of GBS from the murine vagina. However, this was not dependent on functional neutrophil recruitment or CD88 signaling, as EP67 treatment reduced the vaginal bacterial load in mice lacking CD88 or the major neutrophil receptor CXCr2. Interestingly, we found that EP67 inhibits GBS growth in vitro and in vivo and that antibacterial activity was specific to Streptococcus species. Our work establishes that EP67-mediated clearance of GBS is likely due to direct bacterial killing rather than to enhanced immune stimulation. We conclude that EP67 may have potential as a therapeutic to control GBS vaginal colonization. PMID:23979760
Non-infectivity of Cattle Streptococcus agalactiae in Nile Tilapia, Oreochromis niloticus and Channel Catfish, Ictalurus punctatus
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus agalactiae is classified as a Lancefield's group B Streptococcus (GBS). It is the causative bacterium of streptococcosis that is responsible for severe economic losses in wild and cultured fish, worldwide. Streptococcus agalactiae also causes bovine mastitis. Only limited comparativ...
A comparative investigation of Streptococcus agalactiae isolates from fish and cattle
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus agalactiae is the causative bacterium of streptococcosis and causes severe economic losses in wild and cultured fish and cattle, worldwide. In fish, infection can result in septicemia with hemorrhages on the body surface and in the external and internal organs. Streptococcus agalacti...
Hypopituitarism as consequence of late neonatal infection by Group B streptococcus: a case report
Ferreira, Amanda Santana; Fernandes, Ana Lourdes Lima Araújo; Guaragna-Filho, Guilherme
Hypopituitarism is a condition characterized by dysfunction of the pituitary gland hormone production. The insults of the perinatal period, which includes the late infection by Group B Streptococcus, consists in a rare etiology of this condition. We present the case of a 39-days-old infant with meningitis caused by Streptococcus Group B, which showed, among other consequences, hypopituitarism.
Identification of a pheA gene associated with Streptococcus mitis by using suppression subtractive hybridization.
Park, Hee Kuk; Dang, Hien Thanh; Myung, Soon Chul; Kim, Wonyong
We performed suppression subtractive hybridization to identify genomic differences between Streptococcus mitis and Streptococcus pneumoniae. Based on the pheA gene, a primer set specific to S. mitis detection was found in 18 out of 103 S. mitis-specific clones. Our findings would be useful for discrimination of S. mitis from other closely related cocci in the oral environment. PMID:22307284
Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms
Erin Honsa; Thomas Fricke; Alex J Stephens; Danny Ko; Fanrong Kong; Gwendolyn L Gilbert; Flavia Huygens; Philip M Giffard
BACKGROUND: Streptococcus agalactiae (Group B Streptococcus (GBS)) is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP) based method for assigning GBS isolates to multilocus sequence typing (MLST)-defined clonal complexes.
Analysis of the in vitro adherence of Streptococcus mutans and Candida albicans
Dicler de Sant'Anna Vitor Barbieri; Vânia Aparecida Vicente; Fabian Calixto Fraiz; Osmir José Lavoranti; Terezinha Inęs Estivalet Svidzinski; Rosângela Lameira Pinheiro
The objective of the present study was to investigate the in vitro adherence capacity of Streptococcus mutans and Candida albicans. Adherence assays were conducted on dental surfaces and analyzed by scanning electron microscopy (SEM). Extracted human teeth were inoculated with Streptococcus mutans or Candida albicans and with both species simultaneously, and incubated at 37şC for 21 days. Bacterial inocula had
Comparative genomic analyses of Streptococcus mutans provide insights into chromosomal shuffling and species-specific content
Fumito Maruyama; Mitsuhiko Kobata; Ken Kurokawa; Keishin Nishida; Atsuo Sakurai; Kazuhiko Nakano; Ryota Nomura; Shigetada Kawabata; Takashi Ooshima; Kenta Nakai; Masahira Hattori; Shigeyuki Hamada; Ichiro Nakagawa
BACKGROUND: Streptococcus mutans is the major pathogen of dental caries, and it occasionally causes infective endocarditis. While the pathogenicity of this species is distinct from other human pathogenic streptococci, the species-specific evolution of the genus Streptococcus and its genomic diversity are poorly understood. RESULTS: We have sequenced the complete genome of S. mutans serotype c strain NN2025, and compared it
Colonization Rate of Group B Streptococcus (GBS) in Pregnant Women Using GBS Agar Medium
Farnaz Fatemi; Leili Chamani-Tabriz; Parviz Pakzad; Hodjat Zeraati; Hodjatollah Rabbani; Soheila Asgari
Group B streptococci (GBS) or Streptococcus agalactiae are members of the normal flora of the female genital tract. GBS normally colonizes the vagina in many women asymptomatically. During labor this organism may infect the newborn, leading to neonatal sepsis and meningitis. This study aimed to investigate the prevalence of group B streptococcus in pregnant women by a rapid and easy
Suzuki Kurokawa, M; Suzuki, N
Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease. PMID:15598081
INFLUENCE OF NATURAL TRICHODINA SP.PARASITISM ON EXPERIMENTAL STREPTOCOCCUS INIAE OR Streptococcus AGALACTIAE INFECTION AND SURVIVAL OF YOUNG CHANNEL CATFISH ICTALURUS PUNCTATUS (RAFINESQUE)
Technology Transfer Automated Retrieval System (TEKTRAN)
Streptococcus iniae and S. agalactiae are usually not considered pathogens of channel catfish, Ictalurus punctatus, though concurrent infections may decrease catfish survival when infected with streptococcal organisms. Non-parasitized or naturally-parasitized channel catfish fry were challenged wit...
Identification of Streptococcus agalactiae and other Streptococcus species associated with bovine mastitis and the reactivity of a bovine anti-galactosyl antibody with their surface carbohydrates
Turner, Debra D.
Fifteen isolates of Streptococcus species including six reference strains of S. agalactiae were obtained and their surface carbohydrates were examined for their galactosyl linkage properties using an anti-alpha galactosyl antibody purified from calf...
Gene cloning and characterization of MdeA, a novel multidrug efflux pump in Streptococcus mutans.
Kim, Do Kyun; Kim, Kyoung Hoon; Cho, Eun Ji; Joo, Seoung-Je; Chung, Jung-Min; Son, Byoung Yil; Yum, Jong Hwa; Kim, Young-Man; Kwon, Hyun-Ju; Kim, Byung-Woo; Kim, Tae Hoon; Lee, Eun-Woo
Multidrug resistance, especially multidrug efflux mechanisms that extrude structurally unrelated cytotoxic compounds from the cell by multidrug transporters, is a serious problem and one of the main reasons for the failure of therapeutic treatment of infections by pathogenic microorganisms as well as of cancer cells. Streptococcus mutans is considered one of the primary causative agents of dental caries and periodontal disease, which comprise the most common oral diseases. A fragment of chromosomal DNA from S. mutans KCTC3065 was cloned using Escherichia coli KAM32 as host cells lacking major multidrug efflux pumps. Although E. coli KAM32 cells were very sensitive to many antimicrobial agents, the transformed cells harboring a recombinant plasmid became resistant to several structurally unrelated antimicrobial agents such as tetracycline, kanamycin, rhodamin 6G, ampicillin, acriflavine, ethidium bromide, and tetraphenylphosphonium chloride. This suggested that the cloned DNA fragment carries a gene encoding a multidrug efflux pump. Among 49 of the multidrug-resistant transformants, we report the functional gene cloning and characterization of the function of one multidrug efflux pump, namely MdeA from S. mutans, which was expressed in E. coli KAM32. Judging from the structural and biochemical properties, we concluded that MdeA is the first cloned and characterized multidrug efflux pump using the proton motive force as the energy for efflux drugs. PMID:23462018
[Occurrence and diagnostic relevance of virulence-associated factors in Streptococcus suis].
Baums, C G; Da Silva, L M; Goethe, R; Valentin-Weigand, P
Streptococcus suis (Sc. suis) can cause very different clinical entities. In contrast to Sc. suis-associated pneumonia, the induction of meningitis, septicemia, and polyarthritis by certain Sc. suis strains requires the expression of virulence factors that contribute to the invasiveness of the pathogen. In the presented study, we examined the occurrence of known virulence-associated factors in Sc. suis isolates from samples sent to the Institute of Microbiology, School of Veterinary Medicine Hannover, in order to evaluate their significance as potential virulence factors in different disease complexes in Northern Germany. The results show that (i) MRP + EF + serotype 2 and MRP* EF-serotype 9 strains are statistically significant associated with the disease complex meningitis/septicemia/arthritis and, thus, have to be considered invasive strains, (ii) serotyping alone is not sufficient for identification of virulent strains, (iii) there is a remarkable heterogeneity among pneumonia-associated Sc. suis strains and (iv) activity of haemolysin or suilysin appears to be not appropriate as virulence marker. Finally, it has to be noted that at present only half of the Sc. suis isolates from pigs with meningitis/septicemia/poyarthritis can be characterised by the detection of virulence-associated factors. Thus, the identification and characterisation of additional, serotype independent virulence factors of Sc. suis is a very important issue in future studies. PMID:14560446
No Impairment in Host Defense against Streptococcus pneumoniae in Obese CPEfat/fat Mice
Mancuso, Peter; O?Brien, Edmund; Prano, Joseph; Goel, Deepti; Aronoff, David M.
In the US and globally, dramatic increases in the prevalence of adult and childhood obesity have been reported during the last 30 years. In addition to cardiovascular disease, type II diabetes, and liver disease, obesity has recently been recognized as an important risk factor for influenza pneumonia. During the influenza pandemic of 2009, obese individuals experienced a greater severity of illness from the H1N1 virus. In addition, obese mice have also been shown to exhibit increased lethality and aberrant pulmonary inflammatory responses following influenza infection. In contrast to influenza, the impact of obesity on bacterial pneumonia in human patients is controversial. In this report, we compared the responses of lean WT and obese CPEfat/fat mice following an intratracheal infection with Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. At 16 weeks of age, CPEfat/fat mice develop severe obesity, hyperglycemia, elevated serum triglycerides and leptin, and increased blood neutrophil counts. There were no differences between lean WT and obese CPEfat/fat mice in survival or lung and spleen bacterial burdens following intratracheal infection with S. pneumoniae. Besides a modest increase in TNF-? levels and increased peripheral blood neutrophil counts in CPEfat/fat mice, there were not differences in lung or serum cytokines after infection. These results suggest that obesity, accompanied by hyperglycemia and modestly elevated triglycerides, at least in the case of CPEfat/fat mice, does not impair innate immunity against pneumococcal pneumonia. PMID:25203099
Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.
Brown, Armand O; Mann, Beth; Gao, Geli; Hankins, Jane S; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I; Halade, Ganesh V; Mortensen, Eric M; Lindsey, Merry L; Hanes, Martha; Happel, Kyle I; Nelson, Steve; Bagby, Gregory J; Lorent, Jose A; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J; Tuomanen, Elaine I; Orihuela, Carlos J
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1? was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870
Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function
Brown, Armand O.; Mann, Beth; Gao, Geli; Hankins, Jane S.; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I.; Halade, Ganesh V.; Mortensen, Eric M.; Lindsey, Merry L.; Hanes, Martha; Happel, Kyle I.; Nelson, Steve; Bagby, Gregory J.; Lorent, Jose A.; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J.; Tuomanen, Elaine I.; Orihuela, Carlos J.
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1? was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870
Recombination Drives Genetic Diversification of Streptococcus dysgalactiae Subspecies equisimilis in a Region of Streptococcal Endemicity
McMillan, David J.; Kaul, Santosh Y.; Bramhachari, P. V.; Smeesters, Pierre R.; Vu, Therese; Karmarkar, M. G.; Shaila, Melkote S.; Sriprakash, Kadaba S.
Infection of the skin or throat by Streptococcus dysgalactiae subspecies equisimilis (SDSE) may result in a number of human diseases. To understand mechanisms that give rise to new genetic variants in this species, we used multi-locus sequence typing (MLST) to characterise relationships in the SDSE population from India, a country where streptococcal disease is endemic. The study revealed Indian SDSE isolates have sequence types (STs) predominantly different to those reported from other regions of the world. Emm-ST combinations in India are also largely unique. Split decomposition analysis, the presence of emm-types in unrelated clonal complexes, and analysis of phylogenetic trees based on concatenated sequences all reveal an extensive history of recombination within the population. The ratio of recombination to mutation (r/m) events (11?1) and per site r/m ratio (41?1) in this population is twice as high as reported for SDSE from non-endemic regions. Recombination involving the emm-gene is also more frequent than recombination involving housekeeping genes, consistent with diversification of M proteins offering selective advantages to the pathogen. Our data demonstrate that genetic recombination in endemic regions is more frequent than non-endemic regions, and gives rise to novel local SDSE variants, some of which may have increased fitness or pathogenic potential. PMID:21857905
Characterization of Pneumonia Due to Streptococcus equi subsp. zooepidemicus in Dogs?
Priestnall, Simon L.; Erles, Kerstin; Brooks, Harriet W.; Cardwell, Jacqueline M.; Waller, Andrew S.; Paillot, Romain; Robinson, Carl; Darby, Alistair C.; Holden, Matthew T. G.; Schöniger, Sandra
Streptococcus equi subsp. zooepidemicus has been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis of S. equi subsp. zooepidemicus infection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected with S. equi subsp. zooepidemicus. An objective scoring system demonstrated that S. equi subsp. zooepidemicus caused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF, szeN, and szeP) were detected by PCR in 17/47 (36.2%) of the S. equi subsp. zooepidemicus isolates; however, there was no association between the presence of these genes and the histopathological score. The lungs of S. equi subsp. zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-?), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease. PMID:20861329
Isolation of Streptococcus agalactiae and an aquatic birnavirus from doctor fish Garra rufa L
Background The doctor fish, Garra rufa, has become increasingly popular as a treatment for skin disorders and for pedicures in recent years. Despite this there is very little information available regarding the welfare of these fish and the range of potential pathogens they may carry. In this study, a group of fish suffering from post-transport mortalities were examined and the isolated pathogens identified. Findings Group B Streptococcus agalactiae was isolated from kidney swabs of the fish and found to be resistant to a number of antibiotics. In addition to this, a fish virus belonging to the aquabirnavirus group, serogroup C was isolated for the first time in Ireland. However, no clinical signs of disease typical of bacterial or viral infections were observed in any fish examined. Conclusions As no clinical signs of disease attributable to either of the pathogens identified were found it was concluded that the mortalities were most likely due to transport related stress exacerbated by the presence of the pathogens. Further work is required to assess the suitability of current transport strategies and to examine the potential risk associated with the transport of live ornamental fish. PMID:24028334
Genotypic Profile of Streptococcus suis Serotype 2 and Clinical Features of Infection in Humans, Thailand
Kerdsin, Anusak; Dejsirilert, Surang; Puangpatra, Parichart; Sripakdee, Saowalak; Chumla, Koranan; Boonkerd, Nitsara; Polwichai, Pitimol; Tanimura, Susumu; Takeuchi, Dan; Nakayama, Tatsuya; Nakamura, Shota; Akeda, Yukihiro; Gottschalk, Marcelo; Sawanpanyalert, Pathom
To examine associations between clinical features of Streptococcus suis serotype 2 infections in humans in Thailand and genotypic profiles of isolates, we conducted a retrospective study during 2006–2008. Of 165 patients for whom bacterial cultures of blood, cerebrospinal fluid, or both were positive for S. suis serotype 2, the major multilocus sequence types (STs) found were ST1 (62.4%) and ST104 (25.5%); the latter is unique to Thailand. Clinical features were examined for 158 patients. Infections were sporadic; case-fatality rate for adults was 9.5%, primarily in northern Thailand. Disease incidence peaked during the rainy season. Disease was classified as meningitis (58.9%) or nonmeningitis (41.1%, and included sepsis [35.4%] and others [5.7%]). Although ST1 strains were significantly associated with the meningitis category (p<0.0001), ST104 strains were significantly associated with the nonmeningitis category (p<0.0001). The ST1 and ST104 strains are capable of causing sepsis, but only the ST1 strains commonly cause meningitis. PMID:21529392
Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice
Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.
ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845
Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.
Olsen, Randall J; Ashraf, Madiha; Gonulal, Vedia E; Ayeras, Ara A; Cantu, Concepcion; Shea, Patrick R; Carroll, Ronan K; Humbird, Tammy; Greaver, Jamieson L; Swain, Jody L; Chang, Ellen; Ragasa, Willie; Jenkins, Leslie; Lally, Kevin P; Blasdel, Terry; Cagle, Philip; Musser, James M
Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract. PMID:20674736
Acquisition of Five High-M r Penicillin-Binding Protein Variants during Transfer of High-Level b-Lactam Resistance from Streptococcus mitis to Streptococcus pneumoniae
Penicillin-resistant isolates of Streptococcus pneumoniae generally contain mosaic genes encoding the low- affinity penicillin-binding proteins (PBPs) PBP2x, PBP2b, and PBP1a. We now present evidence that PBP2a and PBP1b also appear to be low-affinity variants and are encoded by distinct alleles in b-lactam-resistant trans- formants of S. pneumoniae obtained with chromosomal donor DNA from a Streptococcus mitis isolate. Different lineages of
SO-LAAO, a Novel L-Amino Acid Oxidase That Enables Streptococcus oligofermentans To Outcompete Streptococcus mutans by Generating H2O2 from Peptone
Huichun Tong; Wei Chen; Wenyuan Shi; Fengxia Qi; Xiuzhu Dong
Received 13 March 2008\\/Accepted 27 April 2008 We previously demonstrated that Streptococcus oligofermentans suppressed the growth of Streptococcus mutans, the primary cariogenic pathogen, by producing hydrogen peroxide (H2O2) through lactate oxidase activity. In this study, we found that the lox mutant of S. oligofermentans regained the inhibition while growing on peptone-rich plates. Further studies demonstrated that the H2O2 produced on
Modifications reversibles du caractere de la reaction de gram chez E. coli, PS. Aeruginosa et M. pyogenes var. aureus sous l'influence du stearate d'hexaethylene glycol, un detersif non ionique
N. Delmotte; A. Delmotte
Résumé Certains détersifs appartenant aux groupes anioniques et nonioniques font acquérir auE. coli et auPs. aeruginosa un caractčre Gram positif. Seul, le stéarate d[hexaéthylčne glycol, détersif nonionique négative la réaction de Gram duM. pyogenes var.aureus. Les modifications du caractčre de la réaction de Gram duE. coli, duPs. aeruginosa et duM. pyogenes var.aureus obtenues ŕ l'aide du stéarate d'hexaéthylčne glycol sont réversibles
TetAB(46), a predicted heterodimeric ABC transporter conferring tetracycline resistance in Streptococcus australis isolated from the oral cavity
Warburton, Philip J.; Ciric, Lena; Lerner, Avigdor; Seville, Lorna A.; Roberts, Adam P.; Mullany, Peter; Allan, Elaine
Objectives To identify the genes responsible for tetracycline resistance in a strain of Streptococcus australis isolated from pooled saliva from healthy volunteers in France. S. australis is a viridans Streptococcus, originally isolated from the oral cavity of children in Australia, and subsequently reported in the lungs of cystic fibrosis patients and as a cause of invasive disease in an elderly patient. Methods Agar containing 2 mg/L tetracycline was used for the isolation of tetracycline-resistant organisms. A genomic library in Escherichia coli was used to isolate the tetracycline resistance determinant. In-frame deletions and chromosomal repair were used to confirm function. Antibiotic susceptibility was determined by agar dilution and disc diffusion assay. Results The tetracycline resistance determinant from S. australis FRStet12 was isolated from a genomic library in E. coli and DNA sequencing showed two open reading frames predicted to encode proteins with similarity to multidrug resistance-type ABC transporters. Both genes were required for tetracycline resistance (to both the naturally occurring and semi-synthetic tetracyclines) and they were designated tetAB(46). Conclusions This is the first report of a predicted ABC transporter conferring tetracycline resistance in a member of the oral microbiota. PMID:22941900
Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010 to 2012.
Ikebe, T; Tominaga, K; Shima, T; Okuno, R; Kubota, H; Ogata, K; Chiba, K; Katsukawa, C; Ohya, H; Tada, Y; Okabe, N; Watanabe, H; Ogawa, M; Ohnishi, M
Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused by ?-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60-70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized the emm genotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to be emm1, followed by emm89, emm12, emm28, emm3, and emm90. These six genotypes constituted more than 90% of the STSS isolates. The number of emm1, emm89, emm12, and emm28 isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number of mefA-positive emm1 isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes. PMID:25703404
Effects of phosphoglucomutase gene (PGM) in Streptococcus parauberis on innate immune response and pathogenicity of olive flounder (Paralichthys olivaceus).
Woo, Sung Ho; Park, Soo Il
In recent years, Streptococcus parauberis infection has been an emerging problem in aquaculture in South Korea because of its more frequent isolation than other streptococcal bacteria including Streptococcus iniae. To develop effective treatment and prophylaxis methods against this emerging disease by S. parauberis, it is necessary to understand the underlying pathogenic mechanisms. To uncover the pathogenicity, the mutant strain of S. parauberis with a deleted phosphoglucomutase (PGM) gene which has been known to be an important virulence factor in bacterial pathogens was generated to investigate the relationship between virulence and gene function using an allelic exchange mutagenesis method. Allelic exchange mutagenesis of the phosphoglucomutase gene resulted in phenotype changes including decreased extracellular capsules, reduced buoyancy, increased hydrophobicity and reduced growth. Moreover, the S. parauberis mutant was more sensitive to innate immune clearance mechanisms including serum, mucus and phagocyte killing and could not induce mortality in olive flounder. These phenotype changes and the attenuated virulence of the pathogen to fish could be due to the reduction in capsule production by mutation of the PGM gene. The results provide evidences that phosphoglucomutase expression contributes to S. parauberis virulence in fish by affecting bacterial survival against the host's humoral and cellular defense mechanisms. PMID:25240979
Genomics of Streptococcus salivarius, a major human commensal.
Delorme, Christine; Abraham, Anne-Laure; Renault, Pierre; Guédon, Eric
The salivarius group of streptococci is of particular importance for humans. This group consists of three genetically similar species, Streptococcus salivarius, Streptococcus vestibularis and Streptococcus thermophilus. S. salivarius and S. vestibularis are commensal organisms that may occasionally cause opportunistic infections in humans, whereas S. thermophilus is a food bacterium widely used in dairy production. We developed Multilocus sequence typing (MLST) and comparative genomic analysis to confirm the clear separation of these three species. These analyses also identified a subgroup of four strains, with a core genome diverging by about 10%, in terms of its nucleotide sequence, from that of S. salivarius sensu stricto. S. thermophilus species displays a low level of nucleotide variability, due to its recent emergence with the development of agriculture. By contrast, nucleotide variability is high in the other two species of the salivarius group, reflecting their long-standing association with humans. The species of the salivarius group have genome sizes ranging from the smallest (?1.7Mb for S. thermophilus) to the largest (?2.3Mb for S. salivarius) among streptococci, reflecting genome reduction linked to a narrow, nutritionally rich environment for S. thermophilus, and natural, more competitive niches for the other two species. Analyses of genomic content have indicated that the core genes of S. salivarius account for about two thirds of the genome, indicating considerable variability of gene content and differences in potential adaptive features. Furthermore, we showed that the genome of this species is exceptionally rich in genes encoding surface factors, glycosyltransferases and response regulators. Evidence of widespread genetic exchanges was obtained, probably involving a natural competence system and the presence of diverse mobile elements. However, although the S. salivarius strains studied were isolated from several human body-related sites (all levels of the digestive tract, skin, breast milk, and body fluids) and included clinical strains, no genetic or genomic niche-specific features could be identified to discriminate specific group. PMID:25311532
Specificity of the glucan-binding lectin of Streptococcus cricetus.
Drake, D; Taylor, K G; Bleiweis, A S; Doyle, R J
The specificity of the glucan-binding lectin (GBL) of Streptococcus cricetus AHT was determined. Examination of the kinetics of aggregation of cell suspensions with glucans containing various percentages of alpha-1,6, alpha-1,4, alpha-1,3, and alpha-1,2 anomeric linkages revealed that only glucans with at least 80% alpha-1,6 linkages promoted strong aggregation. Moreover, only linear glucans with molecular weights greater than 5 X 10(5) were capable of causing rapid aggregation of the bacteria. The lectin was observed to be present on S. cricetus strains, on Streptococcus sobrinus, and on several Streptococcus mutants strains. Preincubation of suspensions of S. cricetus AHT with glucan T10 (molecular weight of 10,000) before the addition of high-molecular-weight glucan resulted in competitive inhibition in a concentration-dependent manner. Inhibition was achieved also with isomaltopentaose, isomaltohexaose, and isomaltooctaose, but at higher concentrations than glucan T10. In contrast, no inhibition was observed with maltoheptaose, providing additional evidence for the specificity of GBL. Treatment of suspensions of S. cricetus AHT with trypsin before and after aggregation with high-molecular-weight glucan revealed a substantial level of protection of GBL when in a bound state. Collectively, these results indicated that GBL has an absolute affinity for glucans rich in alpha-1,6 linkages and possesses an active site which recognizes internal sequences and accommodates isomaltosaccharides of at least nine residues. This unusual specificity may contribute to the colonization of S. cricetus, S. sobrinus, and S. mutans in glucan-containing plaque in the oral cavity. Images PMID:3397177
21 CFR 522.1696a - Penicillin G benzathine and penicillin G procaine suspension.
Code of Federal Regulations, 2010 CFR
...pounds of body weight subcutaneously. Repeat dosage in 48 hours. (ii) Conditions of use . (A) Treatment of bacterial pneumonia (Streptococcus spp., Actinomyces pyogenes pyogenes, Staphylococcus aureus ); upper respiratory infections such...
Development of Streptococcus pneumoniae Vaccines Using Live Vectors
Wang, Shifeng; Curtiss, Roy
Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines. PMID:25309747
The Pseudomonas Quinolone Signal Inhibits Biofilm Development of Streptococcus mutans
Inaba, Tomohiro; Oura, Hiromu; Morinaga, Kana; Toyofuku, Masanori; Nomura, Nobuhiko
Bacteria often thrive in natural environments through a sessile mode of growth, known as the biofilm. Biofilms are well-structured communities and their formation is tightly regulated. However, the mechanisms by which interspecies interactions alter the formation of biofilms have not yet been elucidated in detail. We herein demonstrated that a quorum-sensing signal in Pseudomonas aeruginosa (the Pseudomonas quinolone signal; PQS) inhibited biofilm formation by Streptococcus mutans. Although the PQS did not affect cell growth, biofilm formation was markedly inhibited. Our results revealed a unique role for this multifunctional PQS and also indicated its application in the development of prophylactic agents against caries-causing S. mutans. PMID:25854411
Hemin utilization is related to virulence of Streptococcus pneumoniae.
Tai, S S; Lee, C J; Winter, R E
Streptococcus pneumoniae is a causative agent for bacterial pneumonia, otitis media, meningitis, and bacteremia. Mechanisms for acquisition of iron by this organism under low-iron conditions were investigated. Siderophore production was not detected by either chemical or biological methods. Its utilization of iron-containing compounds found in human hosts was tested. Both hemin and hemoglobin supported the full growth of S. pneumoniae in a culture lacking other iron sources, while lactoferrin and transferrin failed to do so. A mutant defective in hemin utilization was isolated and was less virulent than wild-type S. pneumoniae in experimental animals. PMID:8225615
Absence of Streptococcus pneumoniae in pharyngeal swabs of geriatric inpatients.
Jomrich, Nina; Kellner, Silvia; Djukic, Marija; Eiffert, Helmut; Nau, Roland
Colonization of the pharynx by Streptococcus pneumoniae was studied in 185 in-hospital geriatric patients (median age 81 years) from 29 March 2011 to 22 June 2011. Swabs were plated on blood agar plates. Colonies with a morphology suggesting S. pneumoniae were further analyzed. Surprisingly, pneumococci were not found in any of the samples. Pneumococci chronically colonizing the pharynx of elderly people may be much rarer than previously thought and probably are not the source of pneumococcal pneumonia in old age. PMID:25746605
Streptococcus agalactiae, an emerging pathogen for cultured ya-fish, Schizothorax prenanti, in China.
Geng, Y; Wang, K Y; Huang, X L; Chen, D F; Li, C W; Ren, S Y; Liao, Y T; Zhou, Z Y; Liu, Q F; Du, Z J; Lai, W M
Streptococcus agalactiae (Group B streptococcus) has emerged as an important pathogen that affects humans and animals, including aquatic species. S. agalactiae infections are becoming an increasing problem in aquaculture and have been reported worldwide in a variety of fish species, especially those living in warm water. Recently, a very serious infectious disease of unknown aetiology broke out in ya-fish (Schizothorax prenanti) farms in Sichuan Province. A Gram-positive, chain-forming coccus was isolated from moribund cultured ya-fish. The goals of this study were to identify the bacterial strains isolated from diseased fish between 2009 and 2011 in Sichuan Province, China, to evaluate the pathogenicity of the pathogen in ya-fish, crucian carp (Carassius carassius) and the Nile tilapia (Oreochromis niloticus); and to determine the susceptibility of the pathogen strains to many currently available anti-microbial agents. The virulence tests were conducted by intraperitoneal injection of bacterial suspensions. In this study, four strains of a Gram-positive, chain-forming coccus were isolated from moribund cultured ya-fish (S. prenanti). The coccoid microorganism was identified as S. agalactiae using a commercial streptococcal grouping kit and 16S rDNA sequencing analysis. Susceptibility of the isolates to 22 antibiotics was tested using the disc diffusion method. All isolates showed a similar antibiotic susceptibility, which were sensitive to amoxicillin, ciprofloxacin, lomefloxacin, chloramphenicol, rifampin, vancomycin, azithromycin, florfenicol, cefalexin, cefradine and deoxycycline and resistant to gentamicin, sinomin (SMZ/TMP), penicillin, tenemycin, fradiomycin and streptomycin. Furthermore, the virulence tests were conducted by intraperitoneal injection of the isolated strain GY101 in ya-fish, crucian carp and the Nile tilapia. This coccus was lethal to ya-fish, Nile tilapia and crucian carp. The mortality rates of infected ya-fish were 100%, 100%, 60% and 20% at doses of 1.0?×?10?, 1.0?×?10?, 1.0?×?10? and 1.0?×?10? CFU/fish, respectively. The values were 100%, 80%, 60% and 30% for Nile tilapia and 100%, 60%, 10% and 0% for crucian carp. To our knowledge, this is the first report of S. agalactiae as a pathogen of ya-fish. PMID:22146014
Comparative transcriptomic analysis of streptococcus pseudopneumoniae with viridans group streptococci
Background Streptococcus pseudopneumoniae, is a novel member of the genus Streptococcus, falling close to related members like S. pneumoniae, S. mitis, and S. oralis. Its recent appearance has shed light on streptococcal infections, which has been unclear till recently. In this study, the transcriptome of S. pseudopneumoniae CCUG 49455T was analyzed using the S. pneumoniae R6 microarray platform and compared with those of S. pneumoniae KCTC 5080T, S. mitis KCTC 3556T, and S. oralis KCTC 13048T strains. Results Comparative transcriptome analysis revealed the extent of genetic relatedness among the species, and implies that S. pseudopneumoniae is the most closely related to S. pneumoniae. A total of 489, 444 and 470 genes were upregulated while 347, 484 and 443 were downregulated relative to S. pneumoniae in S. pseudopneumoniae, S. oralis and S. mitis respectively. Important findings were the up-regulation of TCS (two component systems) and transposase which were found to be specific to S. pseudopneumoniae. Conclusions This study provides insight to the current understanding of the genomic content of S. pseudopneumoniae. The comparative transcriptome analysis showed hierarchical clustering of expression data of S. pseudopneumoniae with S. pneumoniae and S. mitis with S. oralis. This proves that transcriptional profiling can facilitate in elucidating the genetic distance between closely related strains. PMID:22607240
Characterisation of Streptococcus suis isolates from wild boars (Sus scrofa).
Sánchez del Rey, Verónica; Fernández-Garayzábal, José F; Mentaberre, Gregorio; Briones, Víctor; Lavín, Santiago; Domínguez, Lucas; Gottschalk, Marcelo; Vela, Ana Isabel
Wild boar are widely distributed throughout the Iberian Peninsula and can carry potentially virulent strains of Streptococcus suis. The objective of this study was to determine the prevalence of S. suis in wild boars from two large geographical regions of Spain. Serotypes 1, 2, 7 and 9 identified were further genetically characterised by virulence-associated genotyping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine the population structure of S. suis carried by these animals. Streptococcus suis was isolated from 39.1% of the wild boars examined: serotype 9 was the most frequently isolated (12.5%), followed by serotype 1 (2.5%). Serotype 2 was rarely isolated (0.3%). Eighteen additional serotypes were identified indicating wide diversity of this pathogen within the wild boar population. This heterogeneity was confirmed by PFGE and MLST analyses and the majority of isolates exhibited the virulence-associated genotype mrp-/epf-/sly-. The results of this study highlight that the carriage of S. suis by wild boars is commonplace. However, MLST data indicate that these isolates are not related to prevalent clonal complexes ST1, ST16, ST61 and ST87 typically associated with infection of pigs or humans in Europe. PMID:24726078
Colonization and cariogenicity of Streptococcus ferus in rats.
Coykendall, A L; Freedman, M L
Streptococcus ferus, which is indigenous to wild rats, is a member of the mutans group of streptococci. We tested its ability to colonize and to cause caries in laboratory rats by comparing two strains of S. ferus with the very cariogenic Streptococcus sobrinus strain 6715. Groups of rats were fed either finely ground mouse chow or a 56% sucrose diet, or they were switched from chow to the sucrose diet. All three strains colonized the mouths of rats regardless of diet. However, the infectants reached higher proportions of the total flora more quickly in the rats consuming sucrose. Similarly, the percentage of the oral flora represented by an infecting organism increased numerically when rats originally fed chow were switched to the sucrose diet. S. ferus formed plaques on the teeth of the rats, but these plaques did not proliferate over smooth tooth surfaces as extensively as did those of S. sobrinus. Although S. ferus colonized and accumulated, it was non-cariogenic in rats fed sucrose compared both with rats fed similarly but infected with S. sobrinus 6715 and with uninfected controls. In vitro measurements suggested the S. ferus produced acid less rapidly than S. sobrinus. Thus, the lack of cariogenicity in S. ferus may result from an inability to form copious plaques on smooth tooth surfaces and from low acid production and, therefore, may represent a natural absence of the pathogenic potential usually inherent in the mutans streptococci. PMID:7216496
The Contribution of Non-human Primate Models to the Development of Human Vaccines
Rivera-Hernandez, Tania; Carnathan, Diane G.; Moyle, Peter M.; Toth, Istvan; West, Nicholas P.; Young, Paul L.; Silvestri, Guido; Walker, Mark J.
The nonhuman primates (NHPs) model in biomedical research has contributed to the study of human infectious, autoimmune, oncogenic, and neurological diseases. This review focuses on the importance of NHP models in vaccine development for tuberculosis, pertussis, Dengue, group A streptococcus (Streptococcus pyogenes) infection, HIV infection, and certain diseases in the elderly (influenza, for example). From understanding disease pathogenesis and mechanisms of protection, to assessing vaccine safety and efficacy, we discuss selected cases where the importance of the use of NHP models is highlighted. PMID:25549702
Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.
Nguyen, D Tien; Louwen, Rogier; Elberse, Karin; van Amerongen, Geert; Yüksel, Selma; Luijendijk, Ad; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L
Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies. PMID:25970287
Sensing of Interleukin-1 Cytokines during Streptococcus pneumoniae Colonization Contributes to Macrophage Recruitment and Bacterial Clearance.
Lemon, Jamie K; Miller, Megan R; Weiser, Jeffrey N
Streptococcus pneumoniae (the pneumococcus), a leading cause of bacterial disease, is most commonly carried in the human nasopharynx. Colonization induces inflammation that promotes the organism's growth and transmission. This inflammatory response is dependent on intracellular sensing of bacterial components that access the cytosolic compartment via the pneumococcal pore-forming toxin pneumolysin. In vitro, cytosolic access results in cell death that includes release of the proinflammatory cytokine interleukin-1? (IL-1?). IL-1 family cytokines, including IL-1?, are secreted upon activation of inflammasomes, although the role of this activation in the host immune response to pneumococcal carriage is unknown. Using a murine model of pneumococcal nasopharyngeal colonization, we show that mice deficient in the interleukin-1 receptor type 1 (Il1r1(-/-)) have reduced numbers of neutrophils early after infection, fewer macrophages later in carriage, and prolonged bacterial colonization. Moreover, intranasal administration of Il-1? promoted clearance. Macrophages are the effectors of clearance, and characterization of macrophage chemokines in colonized mice revealed that Il1r1(-/-) mice have lower expression of the C-C motif chemokine ligand 6 (CCL6), correlating with reduced macrophage recruitment to the nasopharynx. IL-1 family cytokines are known to promote adaptive immunity; however, we observed no difference in the development of humoral or cellular immunity to pneumococcal colonization between wild-type and Il1r1(-/-) mice. Our findings show that sensing of IL-1 cytokines during colonization promotes inflammation without immunity, which may ultimately benefit the pneumococcus. PMID:26034210
Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin.
Dupont, Aline; Mohamed, Fatima; Salehen, Nur'Ain; Glenn, Sarah; Francescut, Lorenza; Adib, Rozita; Byrne, Simon; Brewin, Hannah; Elliott, Irina; Richards, Luke; Dimitrova, Petya; Schwaeble, Wilhelm; Ivanovska, Nina; Kadioglu, Aras; Machado, Lee R; Andrew, Peter W; Stover, Cordula
Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause severe infectious disease in human, were used to infect properdin-deficient and wildtype mice. The aim was to deduce a role for properdin, positive regulator of the alternative pathway of complement activation, by comparing and contrasting the immune response of the two genotypes in vivo. We show that properdin-deficient and wildtype mice mounted antipneumococcal serotype-specific IgM antibodies, which were protective. Properdin-deficient mice, however, had increased survival in the model of streptococcal pneumonia and sepsis. Low activity of the classical pathway of complement and modulation of Fc?R2b expression appear to be pathogenically involved. In listeriosis, however, properdin-deficient mice had reduced survival and a dendritic cell population that was impaired in maturation and activity. In vitro analyses of splenocytes and bone marrow-derived myeloid cells support the view that the opposing outcomes of properdin-deficient and wildtype mice in these two infection models is likely to be due to a skewing of macrophage activity to an M2 phenotype in the properdin-deficient mice. The phenotypes observed thus appear to reflect the extent to which M2- or M1-polarised macrophages are involved in the immune responses to S. pneumoniae and L. monocytogenes. We conclude that properdin controls the strength of immune responses by affecting humoral as well as cellular phenotypes during acute bacterial infection and ensuing inflammation. PMID:24728387
Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses
Wilson, R; Cohen, J M; Jose, R J; de Vogel, C; Baxendale, H; Brown, J S
Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis. PMID:25354319