title: Carbapenem resistance in clinical isolates of Pseudomonas aeruginosa.
abstract: The objectives of this study were to identify the carbapenem resistance mechanisms of clinical Pseudomonas aeruginosa isolates. The strains resistant to imipenem had lost only the OprD protein, the isolates resistant to imipenem and meropenem had both loss of the OprD porin and reduced minimum inhibitory concentrations (MICs) in the presence of efflux pump inhibitors. In the isolates in which efflux had been identified (n=2) only 1 isolate had a mutation in the mexR gene corresponding to a glutamine to a stop codon change at amino acid 106. This has not been previously identified. There were no significant changes in the mexT genes. No mutations previously associated with the upregulation of the carbapenem efflux pumps in in vitro generated resistant isolates were identified in any of the clinical isolates. Therefore, the resistance mechanisms identified by development of carbapenem resistance in vitro are not sufficient to understand carbapenem resistance development in clinical isolates.
authors.affiliation: University of Edinburgh, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Walsh
authors.forename: S G B
authors.initials: SG
authors.lastname: Amyes
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D015780:Carbapenems / Q000494:pharmacology*; D018388:Codon, Terminator / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005973:Glutamine / Q000235:genetics; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D018272:Porins / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013845:Thienamycins / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D018388:Codon, Terminator; C423620:MexR protein, Pseudomonas aeruginosa; D018272:Porins; D012097:Repressor Proteins; D013845:Thienamycins; D005973:Glutamine; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D000077731:Meropenem