title: Mutational inactivation of OprD in carbapenem-resistant Pseudomonas aeruginosa isolates from Korean hospitals.
abstract: This study investigated the mechanisms underlying the carbapenem resistance of bloodstream isolates of Pseudomonas aeruginosa obtained from two Korean hospitals. Of the 79 P. aeruginosa isolates, 22 and 21 were resistant to imipenem and meropenem, respectively. The 22 imipenem-resistant P. aeruginosa isolates were classified into 7 sequence types (STs) and 13 pulsotypes. Twelve imipenem-resistant isolates from one hospital were found to belong to the international clone ST111. Two imipenem-resistant P. aeruginosa ST235 isolates carried the bla IMP-6 gene, but the remaining 20 isolates did not produce carbapenemases. Mutations in the oprD gene and a related decrease in gene expression were found in 21 and 5 isolates, respectively. However, all imipenemresistant P. aeruginosa isolates showed no significant expression of OprD in the outer membrane as compared with that of carbapenem-susceptible PAO1 strain. Overexpression of genes associated with efflux pumps, including mexB, mexD, mexF, and mexY, was not found in any imipenem-resistant isolate. One imipenem-resistant P. aeruginosa isolate overexpressed the ampC gene. Our results show that the low permeability of drugs due to the mutational inactivation of OprD is primarily responsible for carbapenem resistance in bloodstream isolates of P. aeruginosa from Korean hospitals.
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Chi Hyun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Jeon
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Yoo Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Dong-A University, College of Medicine, Busan, 602-714, Republic of Korea.
authors.forename: Sang Hwa
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea. leejc@knu.ac.kr.
authors.forename: Je Chul
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018272:Porins / Q000235:genetics*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D056910:Republic of Korea; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D015378:Imipenem; D000077731:Meropenem; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D018272:Porins; D013845:Thienamycins; D001618:beta-Lactamases; C077157:OprD protein, Pseudomonas aeruginosa; C048795:AmpC beta-lactamases; C063912:carbapenemase
keywords: OprD protein; carbapenem; efflux pump; international clone; sequence type