Increased susceptibility to beta-lactam antibiotics and decreased porin content caused by envB mutations of Salmonella typhimurium.
Isogenic derivatives carrying envB6, envB9, or envB+ alleles were obtained from a strain of Salmonella typhimurium that was partially resistant to mecillinam, a beta-lactam antibiotic specific for penicillin-binding protein 2 (PBP 2). Testing of the isogenic strains with several antibacterial agents demonstrated that envB mutations either increased resistance (mecillinam) or did not affect the response (imipemen) to beta-lactams that act primarily on PBP 2, while susceptibilities to beta-lactams that act on PBP 1B, PBP 3, or both were increased. Furthermore, the susceptibilities of envB strains to hydrophobic compounds such as rifampin, novobiocin, or chloramphenicol were not modified, even though their susceptibilities to deoxycholate and crystal violet were enhanced. Outer cell membranes of envB mutants presented a 50% reduction in protein content compared with that of the isogenic envB+ strains, and OmpF and OmpD porins were particularly affected by the reduction. No alteration in the amount or pattern of periplasmic proteins was noticed, and lipopolysaccharides from envB mutants appeared to be normal by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis. By using derivatives that produced a plasmid-encoded beta-lactamase, it was demonstrated that envB cells are slightly less permeable to cephalothin than envB+ bacteria are. It is concluded that the high susceptibility of envB mutants to beta-lactams is due to the increased effectiveness of the antibiotics on PBP 1B, PBP 3, or both.
Oppezzo
O J
OJ
Departamento de Radiobiología, Comisión Nacional de Energía Atómica, Buenos Aires, Argentina.
Avanzati
B
B
Antón
D N
DN
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D008826:Microbial Sensitivity Tests; D010539:Permeability; D018272:Porins; D012475:Salmonella / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D018272:Porins; D047090:beta-Lactams; D001618:beta-Lactamases