Efflux pump overexpression in conjunction with alternation of outer membrane protein may induce Acinetobacter

LiuLin Luo1, XiaoFei Jiang, Qiong Wu

  • 1Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai, China.

Chemotherapy
|February 25, 2011
PubMed
Abstract

Insights

Outer membrane protein downregulation and efflux pump overexpression contribute to imipenem resistance in Acinetobacter baumannii. This study investigated these mechanisms in resistant strains.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Investigating mechanisms of imipenem resistance in Acinetobacter baumannii.
  • Examining the role of outer membrane proteins in antibiotic resistance.

Purpose of the Study:

  • To elucidate the contribution of outer membrane proteins and efflux pumps to imipenem resistance in Acinetobacter baumannii.
  • To compare protein expression profiles between imipenem-sensitive and resistant strains.

Main Methods:

  • Procurement of imipenem-sensitive and resistant Acinetobacter baumannii strains from the same patient.
  • Utilizing multilocus sequence typing and repetitive extragenic palindromic PCR for strain characterization.
  • Employing isoelectric focusing, mass spectrophotometry, and mRNA expression analysis to identify differentially expressed proteins and genes.

Main Results:

  • No carbapenemases (OXA or metallo-β-lactamases) were detected.
  • Downregulation of outer membrane proteins OprD and CarO, and upregulation of a 34-kDa efflux pump protein in the resistant strain.
  • Evidence suggests efflux pump involvement in imipenem resistance, supported by decreased minimum inhibitory concentration (MIC) in the presence of an inhibitor and increased mRNA expression of the efflux pump gene.

Conclusions:

  • Outer membrane protein downregulation and efflux pump overexpression are suggested mechanisms for in vivo induced imipenem resistance in Acinetobacter baumannii.
  • Efflux pump activity plays a significant role in the development of carbapenem resistance.

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