Study of the correlation of imipenem resistance with efflux pumps AdeABC, AdeIJK, AdeDE and AbeM in clinical isolates of Acinetobacter baumannii

Chemotherapy. 2012;58(2):152-8. doi: 10.1159/000335599. Epub 2012 May 16.

Abstract

Background: To investigate the role of efflux pumps AdeABC, AdeIJK, AdeDE and AbeM in reduced susceptibility to imipenem in clinical isolates of Acinetobacter baumannii.

Methods: Susceptibility testing was conducted by the agar dilution method. The presence and expression of pump genes were analyzed by conventional PCR and real-time RT-PCR, respectively.

Results: Most antibiotics, including carbapenem, aminoglycosides, fluoroquinolones and cephalosporins showed high minimum inhibitory concentration (MIC) values in imipenem-resistant A. baumannii (IRAB). After exposure to the efflux pump inhibitor Phe-Arg-β-naphthylamide, a 4- to 32-fold reduction of imipenem MICs was observed in 33 (66%) isolates of IRAB, while no significant decrease occurred in imipenem-susceptible A. baumannii (ISAB). The majority of IRAB isolates (>80%) were found to be positive for adeB, adeR, adeS, adeJ and abeM. Positive adeE was discovered in 6 isolates of IRAB and coexisted with adeB. Approximate 4-, 3- and 11-fold increases in adeB, adeJ and abeM expression were observed, respectively, in IRAB compared to those in ISAB.

Conclusions: A variety of efflux pump systems, including AdeABC, AdeIJK and AbeM, seem to play important roles in the resistance to imipenem of A. baumannii. Moreover, this is the first time that adeE has been found to coexist with adeB in a small number of isolates of A. baumannii.

MeSH terms

  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / isolation & purification
  • Acinetobacter baumannii / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial / drug effects*
  • Humans
  • Imipenem / pharmacology*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Real-Time Polymerase Chain Reaction

Substances

  • AdeA protein, Acinetobacter baumannii
  • AdeB protein, Acinetobacter baumannii
  • AdeC protein, Acinetobacter baumannii
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Imipenem