Lack of efflux mechanism in a clinical isolate of Pseudomonas aeruginosa highly resistant to beta-lactams and imipenem.
An isolate of Pseudomonas aeruginosa from cystic fibrosis was highly resistant to beta-lactams and beta-lactamase inhibitors. The resistant determinants of clinical isolate to imipenem, ceftazidim, cefriaxone and cefepime were conjugally nontransferable. The slow or nonenzymically mediated breakdown of imipenem and other broad-spectrum beta-lactams suggested the resistance of P. aeruginosa isolate to these drugs which may be attributed to both permeability and efflux. Impaired penetration of imipenem and other beta-lactams through the membrane was detected by a diminished expression of outer-membrane proteins of approximate molar mass of 46 and 39 kDa, matched to OprD and OprF, respectively. Efflux resistance mechanism for meropenem and beta-lactams has been ruled out since the isolate failed to express outer-membrane protein of approximately 50 kDa which is matched to the OprM protein channel. Thus, reduced permeability in the clinical isolate is the main mechanism conferring resistance against beta-lactams including imipenem.
Kadry
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Microbiology Division, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia. akadry@ksu.edu.sa
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001693:Biological Transport, Active; D000077723:Cefepime; D002442:Ceftazidime / Q000378:metabolism / Q000494:pharmacology; D002443:Ceftriaxone / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002511:Cephalosporins / Q000378:metabolism; D003227:Conjugation, Genetic; D003550:Cystic Fibrosis / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005798:Genes, Bacterial; D006801:Humans; D015378:Imipenem / Q000378:metabolism / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002511:Cephalosporins; D026901:Membrane Transport Proteins; C402263:OprM protein, Pseudomonas aeruginosa; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D002443:Ceftriaxone; D000077723:Cefepime; D002442:Ceftazidime