title: Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae.
abstract: BACKGROUND
  Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps.
  
  
  METHODS
  Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC) of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed.
  
  
  RESULTS
  Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates.
  
  
  CONCLUSIONS
  Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae.
authors.affiliation: Department of Respiratory Medicine, An Qiu People's Hospital, An Qiu, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yuhan
authors.affiliation: Department of Respiratory Medicine, An Qiu People's Hospital, An Qiu, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ziyun
authors.affiliation: Department of Respiratory Medicine, An Qiu People's Hospital, An Qiu, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yongbo
authors.affiliation: Department of Clinical Laboratory, Liao Cheng Dong Chang Fu People's Hospital, Liao Cheng, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fuqiang
authors.affiliation: Department of Clinical Laboratory, Yi Shui People's Hospital, Yi Shui, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qinghua
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D058885:Multilocus Sequence Typing; D060888:Real-Time Polymerase Chain Reaction; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline