Molecular mechanisms of AcrB-mediated multidrug export

Res Microbiol. 2018 Sep-Oct;169(7-8):372-383. doi: 10.1016/j.resmic.2018.05.005. Epub 2018 May 25.

Abstract

The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR) in Gram-negative pathogenic bacteria. AcrB is the most thoroughly studied RND transporter and has functioned as a model for our understanding of efflux-mediated MDR. This multidrug-exporter can recognize and transport a wide range of structurally unrelated compounds (including antibiotics, dyes, bile salts and detergents), while it shows a strict inhibitor specificity. Here we discuss our current knowledge of AcrB, and include recent advances, regarding its structure, mechanism of drug transport, substrate recognition, different intramolecular entry pathways and the drug export driven by remote conformational coupling.

Keywords: AcrB; Mechanism; Multidrug-resistance; Pathogens; RND; Structure.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / chemistry
  • Gram-Negative Bacteria / classification
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / metabolism*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins