Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance

Mol Microbiol. 2005 Apr;56(2):323-33. doi: 10.1111/j.1365-2958.2005.04556.x.

Abstract

Recent studies have highlighted the importance of a parasite protein referred to as the chloroquine resistance transporter (PfCRT) in the molecular basis of Plasmodium falciparum resistance to the quinoline antimalarials. PfCRT, an integral membrane protein with 10 predicted transmembrane domains, is a member of the drug/metabolite transporter superfamily and is located on the membrane of the intra-erythrocytic parasite's digestive vacuole. Specific polymorphisms in PfCRT are tightly correlated with chloroquine resistance. Transfection studies have now proven that pfcrt mutations confer verapamil-reversible chloroquine resistance in vitro and reveal their important role in resistance to quinine. Available evidence is consistent with the view that PfCRT functions as a transporter directly mediating the efflux of chloroquine from the digestive vacuole.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chloroquine / pharmacology*
  • Drug Resistance / physiology*
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology*
  • Membrane Transport Proteins / metabolism
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Protozoan Proteins

Substances

  • Ion Channels
  • Membrane Proteins
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine