title: OprD mutations and inactivation in imipenem-resistant Pseudomonas aeruginosa isolates from China.
abstract: To investigate the mechanisms involved in imipenem resistance of Pseudomonas aeruginosa in southern China, 61 imipenem-resistant P. aeruginosa clinical isolates were collected from 4 hospitals between October 2011 and June 2012. All isolates were resistant to imipenem, whereas 21.3% were susceptible or intermediate to meropenem. Variable degrees of resistance to other β-lactam and non-β-lactam antimicrobials were observed. PFGE revealed high-level of clonal diversity. Among the 61 isolates, 50 isolates had OprD loss by disrupted oprD mutations, including 43 with frameshift mutations of oprD and 7 with a premature stop codon by single point mutation. Six isolates were oprD-negative by PCR, suggestive of a major disruption of oprD genes. Five isolates had intact oprD but had reduced expression of oprD genes. In addition, only one isolate with disrupted oprD mutation by a premature stop codon was confirmed to be a metallo-β-lactamase producer (IMP-9). Our results show that the loss of OprD, as well as reduced expression of oprD and MBL production, were the predominant mechanisms of imipenem resistance in P. aeruginosa in southern China.
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Fang
authors.affiliation: Clinical Microbiology Laboratory, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qing
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Cao
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China. Electronic address: tiangb@mail.sysu.edu.cn.
authors.forename: Guo-Bao
authors.initials: GB
authors.lastname: Tian
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China. Electronic address: huangxi6@mail.sysu.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D002681:China; D024881:Drug Resistance, Bacterial; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D018272:Porins / Q000235:genetics* / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D001618:beta-Lactamases / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D018272:Porins; D047090:beta-Lactams; C077157:OprD protein, Pseudomonas aeruginosa; D001618:beta-Lactamases
keywords: Imipenem; Pseudomonas aeruginosa; oprD