Efflux drug transporters at the forefront of antimicrobial resistance

Eur Biophys J. 2017 Oct;46(7):647-653. doi: 10.1007/s00249-017-1238-2. Epub 2017 Jul 14.

Abstract

Bacterial antibiotic resistance is rapidly becoming a major world health consideration. To combat antibiotics, microorganisms employ their pre-existing defence mechanisms that existed long before man's discovery of antibiotics. Bacteria utilise levels of protection that range from gene upregulation, mutations, adaptive resistance, and production of resistant phenotypes (persisters) to communal behaviour, as in swarming and the ultimate defence of a biofilm. A major part of all of these responses involves the use of antibiotic efflux transporters. At the single cell level, it is becoming apparent that the use of efflux pumps is the first line of defence against an antibiotic, as these pumps decrease the intracellular level of antibiotic while the cell activates the various other levels of protection. This frontline of defence involves a coordinated network of efflux transporters. In the future, inhibition of this efflux transporter network, as a target for novel antibiotic therapy, will require the isolation and then biochemical/biophysical characterisation of each pump against all known and new antibiotics. This depth of knowledge is required so that we can fully understand and tackle the mechanisms of developing antimicrobial resistance.

Keywords: Antibiotics; Antimicrobial resistance; Efflux pumps; Efflux transporters; Persister; RND.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological / drug effects
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Biofilms / drug effects
  • Drug Resistance, Bacterial*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*

Substances

  • Anti-Bacterial Agents
  • Membrane Transport Proteins