Structural Insights into Transporter-Mediated Drug Resistance in Infectious Diseases

J Mol Biol. 2021 Aug 6;433(16):167005. doi: 10.1016/j.jmb.2021.167005. Epub 2021 Apr 20.

Abstract

Infectious diseases present a major threat to public health globally. Pathogens can acquire resistance to anti-infectious agents via several means including transporter-mediated efflux. Typically, multidrug transporters feature spacious, dynamic, and chemically malleable binding sites to aid in the recognition and transport of chemically diverse substrates across cell membranes. Here, we discuss recent structural investigations of multidrug transporters involved in resistance to infectious diseases that belong to the ATP-binding cassette (ABC) superfamily, the major facilitator superfamily (MFS), the drug/metabolite transporter (DMT) superfamily, the multidrug and toxic compound extrusion (MATE) family, the small multidrug resistance (SMR) family, and the resistance-nodulation-division (RND) superfamily. These structural insights provide invaluable information for understanding and combatting multidrug resistance.

Keywords: infectious disease; membrane transporters; multidrug resistance; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Anti-Infective Agents / therapeutic use
  • Drug Resistance, Microbial* / genetics
  • Drug Resistance, Multiple
  • Humans
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Structure-Activity Relationship

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Infective Agents
  • Membrane Transport Proteins