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Characterization of vB_Sau_S90, and vB_Sau_S165, a Broad Host Range Phages, and Multiple Phage Doses as a Potential Therapeutic Strategy to Eliminate Transient Phage Resistant Mutants in Staphylococcus Aureus


 Methicillin-Resistant Staphylococcus aureus is a human pathogen. MRSA has acquired resistance to major antibiotics; thus, phage therapy has become a potential alternative treatment. In this work, two broad host range Staphylococcus phages were characterized for lifecycle, physio-chemical parameters and bacterial killing kinetics, and the in vitro behavior of phage insensitive bacterial cells to alternative serial passage and multiple phage doses were assessed by reduction in the bacterial turbidity and spot assay. Phage vB_Sau_S90 showed an absorption efficiency of 91 ± 0.6% with an adsorption time of 17 ± 1 min and vB_Sau_S165 of 95 ± 0.5% adsorption efficiency and 15 ± 2 min adsorption time. Both the phages were stable over a wide range of temperature (20 to 50 ℃) and pH (3 to 11). vB_Sau_S90 phage belonging to the family Siphoviridae [order Caudovirals] showed killing efficiency against 88% (181/205) of S. aureus isolates, and vB_Sau_S165 belonging to family Podoviridae [order Caudovirals] showed killing efficiency against 94% (192/205) of S. aureus isolates. The sensitive and transient phage-resistant cells that remained uninfected during the single dose of phage treatment were eliminated upon a minimum of five alternative serial passage and multiple phage doses. This study concludes that both the phages showed promising activity against methicillin-resistant Staphylococcus aureus. Our study revealed that despite phage auto-dosing and high therapeutic efficiency, both phages did not produce a complete bacterial clearance at a single phage dose; hence indicated that multiple phage doses were required to attain a successful and complete bacterial eradication.