title: Efflux pump overexpression in conjunction with alternation of outer membrane protein may induce Acinetobacter baumannii resistant to imipenem.
abstract: BACKGROUND
  To investigate the role of outer membrane proteins in Acinetobacter baumannii resistant to imipenem, 2 strains were procured from the same patient.
  
  
  METHODS
  The imipenem-resistant strain was obtained following a period of imipenem treatment in vivo. The multilocus sequence typing and repetitive extragenic palindromic PCR results indicated that the imipenem-resistant strain originated from the sensitive one.
  
  
  RESULTS
  Isoelectric focusing detected no carbapenemases, with neither OXA carbapenemases nor metallo-β-lactamases found. Mass spectrophotometric analysis revealed that 3 outer membrane proteins were expressed differentially in the 2 strains: 2 downregulated proteins (OprD and CarO) and 1 upregulated the 34-kDa efflux pump protein in the resistant strain. A 32-fold decrease in the MIC for imipenem in the presence of Phe-Arg-β-naphthylamide in the same strain indicated a possible involvement of the efflux pump mechanism in its resistance, which was consistent with the findings that the mRNA expression of the 34-kDa efflux pump gene was almost fivefold upregulated in the imipenem-resistant strain compared with that in the imipenem-sensitive strain. Such a significant difference, however, was not found in the expression of AdeB and AdeJ between the 2 strains, and AdeE was not detected.
  
  
  CONCLUSIONS
  Our results suggested that downregulation of outer membrane proteins in conjunction with efflux pump overexpression might contribute to imipenem resistance induced in vivo in A. baumannii.
authors.affiliation: Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai, China.
authors.forename: LiuLin
authors.initials: L
authors.lastname: Luo
authors.forename: XiaoFei
authors.initials: X
authors.lastname: Jiang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: LiMing
authors.initials: L
authors.lastname: Wei
authors.forename: JianHua
authors.initials: J
authors.lastname: Li
authors.forename: ChunMei
authors.initials: C
authors.lastname: Ying
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D007525:Isoelectric Focusing; D013058:Mass Spectrometry; D026901:Membrane Transport Proteins / Q000378:metabolism*; D015854:Up-Regulation; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: C445684:AdeB protein, Acinetobacter baumannii; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004151:Dipeptides; D026901:Membrane Transport Proteins; C474925:phenylalanylarginine-naphthylamide; D015378:Imipenem; D001618:beta-Lactamases; C063912:carbapenemase