Beta-lactam-fosfomycin antagonism involving modification of penicillin-binding protein 3 in Pseudomonas aeruginosa.
Antagonism between fosfomycin and antipseudomonal penicillins, cefotaxime, and ceftriaxone was observed in Pseudomonas aeruginosa RYC212. Fosfomycin, a non-beta-lactam antibiotic that acts on bacterial cell wall synthesis, decreased the expression of penicillin-binding protein 3 and induced beta-lactamase. The antagonistic effect was reduced in the presence of high concentrations of the beta-lactamase inhibitor tazobactam or in fosfomycin-resistant mutants. We suggest that products resulting from fosfomycin cell wall damage could interact with a system that regulates penicillin-binding protein and beta-lactamase production.
Reguera
J A
JA
Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain.
Baquero
F
F
Berenguer
J
J
Martinez-Ferrer
M
M
Martinez
J L
JL
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002439:Cefotaxime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D005578:Fosfomycin / Q000037:antagonists & inhibitors*; D006602:Hexosyltransferases / Q000096:biosynthesis / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010458:Peptidyl Transferases / Q000096:biosynthesis / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001618:beta-Lactamases / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D005578:Fosfomycin; D002443:Ceftriaxone; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D002439:Cefotaxime