Bacterial efflux transporters' polyspecificity - a gift and a curse?

Curr Opin Microbiol. 2021 Jun:61:115-123. doi: 10.1016/j.mib.2021.03.009. Epub 2021 Apr 30.

Abstract

All mechanisms of clinical antibiotic resistance benefit from activities of polyspecific efflux pumps acting to reduce intracellular accumulation of toxins and antibiotics. In Gram-negative bacteria, the major polyspecific efflux transporters belong to the Resistance-Nodulation-cell Division (RND) superfamily of proteins, which are capable of expelling thousands of structurally diverse compounds. Recent structural and functional advances generated novel insights into mechanisms underlying the biochemical versatility of RND transporters. This opinion article reviews these mechanisms and discusses implications of the polyspecificity of RND transporters for bacterial survival and for the development of efflux pump inhibitors effective in clinics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biological Transport
  • Drug Resistance, Microbial
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria* / genetics
  • Gram-Negative Bacteria* / metabolism
  • Membrane Transport Proteins* / genetics
  • Membrane Transport Proteins* / metabolism

Substances

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