Susceptibility to Antibiotics and -Lactamase Induction in Murein Hydrolase Mutants of Escherichia coli

The antibiotic susceptibilities and capabilities to induce -lactamases were studied in multiple Escherichia coli murein (peptidoglycan) hydrolase mutants. E. coli mutants lacking either three amidases, three amidases and one lytic transglycosylase, or six lytic transglycosylases showed higher levels of susceptibility to bacitracin, erythromycin, gallidermin, and vancomycin than the wild type. Mutant cells without three amidases lost viability in the presence of vancomycin and gallidermin, whereas the wild type was resistant to both antibiotics. -Lactamase induction was studied after introduction of a plasmid carrying the ampC and ampR genes. Upon addition of cefoxitin to the growth medium, the wild type as well as a mutant lacking all known amidases and DD-endopeptidases induced -lactamase, whereas a mutant lacking all known lytic transglycosylases was unable to induce -lactamase, showing that lytic transglycosylase activity is essential for -lactamase induction. Consequently, cells lacking lytic transglycosylase activity lysed in the presence of penicillin, despite the presence of the inducible -lactamase system. We discuss the potential of murein hydrolase inhibitors for antibiotic therapy.