title: Tigecycline Susceptibility and Molecular Resistance Mechanisms Among Clinical Klebsiella pneumoniae Strains Isolated During Non-Tigecycline Treatment.
abstract: Tigecycline is one of the few therapeutic options that are available for treating serious clinical infections. However, tigecycline nonsusceptible Enterobacteriaceae has emerged recently in China. In this study, a total of 28 clinical Klebsiella pneumoniae isolates that were not previously exposed to tigecycline were collected and confirmed for tigecycline minimum inhibitory concentrations (MICs) using standard broth microdilution tests. To elucidate the mechanisms underlying molecular resistance to tigecycline, the expression levels of efflux pumps AcrAB and OqxAB and their regulators RamA, MarA, RarA, and SoxS were determined by quantitative polymerase chain reaction. The expression levels of the genes acrB, ramA, marA, and soxS were statistically different in different MIC groups (p < 0.05). Sequence analysis of the acrR and ramR genes revealed several nonsynonymous mutations in the nine resistance isolates. The values of MIC in these isolated strains with ramR mutations were significantly higher than those without ramR mutation (p = 0.029). Moreover, mutations in the ramR gene led to the overexpression of RamA. These results indicated that the mutation of the ramR gene through the upregulated expression of RamA contributed to tigecycline resistance and that several of the newly identified types of mutations in ramR and acrR were not previously reported in K. pneumoniae clinical isolates.
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Ruilian
authors.initials: R
authors.lastname: Li
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Yujia
authors.initials: Y
authors.lastname: Han
authors.affiliation: 2 Institute for Chronic and Non-Communicable Disease Prevention and Control , Dalian Center for Disease Prevention and Control, Dalian, China .
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Zemin
authors.initials: Z
authors.lastname: Du
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1 Department of Biotechnology, Dalian Medical University , Dalian, China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics; D002681:China; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000379:methods; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058885:Multilocus Sequence Typing / Q000379:methods; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000078304:Tigecycline; D008911:Minocycline
keywords: Klebsiella pneumoniae; efflux pump; ramR; tigecycline resistance