Is PfCRT a channel or a carrier? Two competing models explaining chloroquine resistance in Plasmodium falciparum.
Chloroquine (CQ), an antimalarial drug with a long history, now frequently fails in the field owing to the rapid spread of resistant Plasmodium falciparum strains. CQ resistance is linked to a K76T mutation in PfCRT, a membrane-located food vacuolar protein and member of the drug-metabolite transporter superfamily, but there is as yet no agreed mechanism of how mutated PfCRT brings about CQ resistance. Current models suggest that mutated PfCRT acts either as a channel or a transporter of CQ, enabling CQ to leave the digestive food vacuole of the parasite, in which the CQ accumulates. Here, we review the pros and cons of the carrier and transporter models in light of recent developments in the field.
Sanchez
Cecilia P
CP
Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Stein
Wilfred D
WD
Lanzer
Michael
M
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D006863:Hydrogen-Ion Concentration; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*
D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine