Efflux-mediated antibiotic resistance in Acinetobacter spp

Sébastien Coyne1, Patrice Courvalin, Bruno Périchon

  • 1Institut Pasteur, Unité des Agents Antibactériens, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.

Insights

Multidrug resistance in Acinetobacter baumannii is significantly driven by increased expression of chromosomal efflux pumps, particularly resistance-nodulation-division (RND) systems, rather than solely gene acquisition.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Acinetobacter baumannii is a major cause of nosocomial infections, especially in intensive care units.
  • Multidrug resistance (MDR) in A. baumannii was previously attributed mainly to acquired resistance genes.
  • Emerging evidence highlights the critical role of increased expression of chromosomal efflux systems in MDR.

Purpose of the Study:

  • To investigate the role of efflux pump gene expression in multidrug resistance in Acinetobacter baumannii.
  • To identify the prevalent efflux pump systems contributing to MDR in this opportunistic pathogen.

Main Methods:

  • Analysis of gene expression levels of various efflux pump systems.
  • Identification of mutations in regulatory genes associated with efflux pump overexpression.
  • Characterization of the substrate range and contribution of different efflux pumps to resistance.

Main Results:

  • Resistance-nodulation-division (RND) systems are the most prevalent pumps in multiply resistant A. baumannii.
  • Overexpression of the AdeABC system, due to mutations in adeRS, is a primary MDR mechanism.
  • Other RND (AdeFGH), non-RND (CraA, AmvA, AbeM, AbeS), and acquired efflux pumps (MFS, SMR) also contribute to resistance.

Conclusions:

  • Increased expression of chromosomal efflux systems, especially RND pumps like AdeABC, is a key driver of MDR in A. baumannii.
  • While intrinsic pumps like AdeIJK contribute to natural resistance, their overexpression is limited by toxicity.
  • Understanding these efflux mechanisms is crucial for developing strategies to combat MDR infections caused by A. baumannii.

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