Transporters involved in resistance to antimalarial drugs.
The ability to treat and control Plasmodium falciparum infection through chemotherapy has been compromised by the advent and spread of resistance to antimalarial drugs. Research in this area has identified the P. falciparum chloroquine resistance transporter (PfCRT) and the multidrug resistance-1 (PfMDR1) transporter as key determinants of decreased in vitro susceptibility to several principal antimalarial drugs. Transfection-based in vitro studies are consistent with clinical findings of an association between mutations in the pfcrt gene and failure of chloroquine treatment, and between amplification of the pfmdr1 gene and failure of mefloquine treatment. Many countries are now switching to artemisinin-based combination therapies. These incorporate partner drugs of which some have an in vitro efficacy that can be modulated by changes in pfcrt or pfmdr1. Here, we summarize investigations of these and other recently identified P. falciparum transporters in the context of antimalarial mode of action and mechanisms of resistance.
Valderramos
Stephanie G
SG
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Fidock
David A
DA
D000818:Animals; D000962:Antimalarials / Q000378:metabolism* / Q000627:therapeutic use; D037621:Artemisinins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002738:Chloroquine / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D000252:Calcium-Transporting ATPases; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D012717:Sesquiterpenes; D017923:Sodium-Hydrogen Exchangers; C513500:ATP6 protein, Plasmodium falciparum; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C031327:artemisinin