Role of OmpD2 and chromosomal beta-lactamase in carbapenem resistance in clinical isolates of Pseudomonas aeruginosa.
Imipenem-resistant clinical isolates of Pseudomonas aeruginosa were divided into two categories: (i) isolates that were moderately resistant to imipenem (MIC 6.25 mg/L) that produced trace amounts of protein D2 detected with immunoblotting using anti-protein D2 antibody, but not when stained with Coomassie blue and had inducible class 1 beta-lactamase expression; (ii) isolates that were highly resistant to several beta-lactams, including meropenem, with no protein D2 by staining or immunoblotting and had stably derepressed beta-lactamase. Laboratory strains were isolated and analyzed: (i) mutants lacking protein D2, or (ii) lacking protein D2 and producing stably derepressed beta-lactamase with carbapenem resistance similar to the clinical isolates. (iii) mutants producing undetectable beta-lactamase which were four-fold more susceptible to imipenem than the mutant producing stably derepressed beta-lactamase or the strain with inducible beta-lactamase. These data suggests that beta-lactamase and outer membrane permeability govern meropenem-resistance in P. aeruginosa.
Satake
S
S
Department of Cellular Information Sciences, Tokai University School of Medicine, Isehara, Japan.
Yoneyama
H
H
Nakae
T
T
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002876:Chromosomes, Bacterial; D004352:Drug Resistance, Microbial; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
D001425:Bacterial Outer Membrane Proteins; D015378:Imipenem; D001618:beta-Lactamases