Implications des pompes membranaires de Plasmodium falciparum dans le transport et la résistance aux antipaludiques

Abstract

The malaria parasite Plasmodium falciparum has become resistant to most antimalarial drugs and even to the latest marketed ones, like artemisinin-based combinaison therapies (ACT) in Southeast Asia. A possible reason for resistance to antimalarial drugs could be that drugs do not reach their target sites, due to active extrusion out of parasite. More than 100 transporters would be localized at the P. falciparum plasmic membrane and digestive vacuole membrane. Some of these transporters, belonging primarily to the superfamily of DMT (drug/metabolite transporters) like PfCRT (Plasmodium falciparum chloroquine resistance transporter) and to the superfamily of ABC transporters (ATP-binding cassette) like PfMDR1 (Plasmodium falciparum multidrug resistance protein 1), PfMDR2, PfMDR5 and PfMDR6, and PfMRP1 (Plasmodium falciparum multidrug resistance-associated protein 1) and PfMRP2, are involved in antimalarial drug transport and drug resistance. Gene amplification or single nucleotide mutations in these genes can modulate P. falciparum susceptibility level to antimalarial drugs. The use of inhibitors against these transporters is a promising novel therapeutic drug strategy.