title: Efflux system overexpression and decreased OprD contribute to the carbapenem resistance among extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa isolates from a Chinese university hospital.
abstract: The aim of this study was to investigate, for the first time, the combinations of carbapenem resistance mechanisms in clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Pseudomonas aeruginosa in a Chinese hospital. Pulsed-field gel electrophoresis revealed the presence of eight clonal types among the 15 ESBL producers. Multilocus sequence typing of two isolates harboured blaIMP-1 identified the clonal strain as ST325. All these genes were found either alone or simultaneously in the strains in the following five different arrangements:<blaOXA-10>; <blaOXA-10, blaIMP-1>; <blaPER-1, blaOXA-10>; <blaPER-1, blaPSE-1>; <blaOXA-10, blaTEM-1>. Regarding mutation-driven resistance, all, but four of the isolates had a relevant decrease of oprD expression. In addition, 73.3% of the isolates overexpressed mexB, 40% mexD, and 33.3% mexY. A specific combination of overexpressed mexB or mexY and alteration in loop L710 of OprD were significantly associated with meropenem resistance. In conclusion, combination of several mutation-driven mechanisms leading to OprD inactivation and overexpression of efflux systems was the main carbapenem resistance mechanism among the ESBL-producing P. aeruginosa isolates, but acquisition of a transferable resistance determinant such as metallo-β-lactamase could be problematic in clinical settings in China.
authors.affiliation: 1 The First Affiliated Hospital of Nanchang University, Nanchang University , Nanchang, People's Republic of China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Li
authors.forename: La-Gen
authors.initials: LG
authors.lastname: Wan
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Jiang
authors.forename: Fang-Qu
authors.initials: FQ
authors.lastname: Li
authors.forename: Jing-Hong
authors.initials: JH
authors.lastname: Yang
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015780:Carbapenems / Q000627:therapeutic use; D002681:China; D002999:Clone Cells; D015964:Gene Expression Regulation, Bacterial; D022761:Gene Transfer, Horizontal; D019450:Genes, MDR; D006785:Hospitals, University; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D058885:Multilocus Sequence Typing; D010957:Plasmids; D018272:Porins / Q000235:genetics* / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D015780:Carbapenems; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C118597:MexB protein, Pseudomonas aeruginosa; C121980:MexD protein, Pseudomonas aeruginosa; C402791:MexXY protein, Pseudomonas aeruginosa; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D001618:beta-Lactamases