title: The mechanism of high-level carbapenem resistance in Klebsiella pneumoniae: underlying Ompk36-deficient strains represent a threat of emerging high-level carbapenem-resistant K. pneumoniae with IMP-1 β-lactamase production in Japan.
abstract: The mechanisms of high-level carbapenem resistance in Klebsiella pneumoniae isolated in Japan were investigated. High-level carbapenem-resistant K. pneumoniae Mkp4437 and a less carbapenem-sensitive K. pneumoniae strain, Mkp4365, were recovered from the same patient. These two strains were found to be homologous by pulsed-field gel electrophoresis, and both strains contained blaIMP-1, blaDHA-1, blaCTXM-14, blaTEM-1, and blaSHV-1. Based on the sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the lack of Ompk36 was observed in Mkp4437. Direct sequencing of the ompK36 gene demonstrated that a new insertional sequence in the open reading frame of the ompK36 gene was found in Mkp4437. Three clinical isolates (minimum inhibitory concentration [MIC] 2-4 mg/L to imipenem) were identified upon screening the strains of K. pneumoniae isolated in the University hospital with MICs of ≥ 1 mg/L to imipenem. Interestingly, these three isolates all lacked OmpK36. Conjugation of the plasmid harboring IMP-1 to these three OmpK36-deficient strains led to the isolation of high-level carbapenem-resistant transconjugants. In conclusion, the mechanisms of high-level carbapenem resistance in K. pneumoniae entail not only the production of IMP-1 β-lactamase but also the lack of OmpK36. It is vital to monitor for the presence of less carbapenem-sensitive K. pneumoniae strains, which lack OmpK36, because blaIMP-1 transmission to these strains may result in isolates with a high-level carbapenem-resistant phenotype.
authors.affiliation: Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. t-sho@med.uoeh-u.ac.jp
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sho
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Muratani
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hamasuna
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yakushiji
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D015780:Carbapenems / Q000494:pharmacology; D003227:Conjugation, Genetic; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D007564:Japan; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D010957:Plasmids; D018272:Porins / Q000172:deficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; C409201:beta-lactamase IMP-1; D001618:beta-Lactamases