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Antibiotic-supersusceptible mutants of Escherichia coli and Salmonella typhimurium

The outer membrane (OM) of many gram-negative bacteria, such as strains of the family Enterobacteriaceae, acts as an effective permeability barrier against various noxious agents, including antibiotics (31, 32, 35, 36, 54). The diffusion of hydrophobic antibiotics through the enterobacterial OM is very restricted because of the lack of glycerophospholipid bilayers, the effective pathway for hydrophobic diffusion (33-35). In addition, large hydrophilic drugs are excluded; they cannot traverse the narrow porin pores, the channels for small hydrophilic nutrients (30-32). The structural integrity of the OM is attributable to its unique lipopolysaccharide (LPS) constituent; adjacent LPS molecules are apparently joined electrostatically by Mg2+, Ca2+, and polyamines to form a stable "roof of tiles" on the surface of the OM (25, 33, 36). Mutants that have a defective OM permeability barrier function are useful in various fields of basic and applied research. The mutagenicity screening tests developed by Ames et al. (1) use LPS-defective deep rough mutants of Salmonella typhimurium; the OM of such strains is a less effective barrier against hydrophobic mutagens than is that of wild-type S. typhimurium. Many probes and drugs used in studies of bacterial cell physiology and biochemistry are hydrophobic and cannot penetrate the wild-type OM but cross the defective OM (34, 35, 54). In biotechnology, bioconversion processes and the production of recombinant proteins in Escherichia coli can greatly benefit from mutants that allow maximal diffusion of substrates and release of synthesized periplasmic proteins, respectively. Finally, the use of OM-defective mutants in antibiotic screening panels has led to the discovery of novel antibacterial substances that are active against gram-negative bacteria and inactive or much less active against gram-positive bacteria (12). This review briefly summarizes the recent salient data on the OM-defective antibiotic-supersusceptible mutants of E. coli and S. typhimurium. Furthermore, the review compares the phenotypes of the mutants and shows that some of the very recently reported mutants carry the most supersusceptible phenotype.