Plasmodium falciparum multidrug resistance protein 1 (PfMDR1)

Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) is an ATP-binding cassette (ABC) transporter localized on the membrane of the parasite’s digestive vacuole and functions as a major determinant of antimalarial drug resistance in malaria-causing parasites[1][3][2]. It actively transports diverse small molecules, including multiple antimalarial drugs, out of the digestive vacuole, thus lowering their concentration at the drug’s site of action. Polymorphisms and increased copy number of pfmdr1 are strongly associated with treatment failures for several frontline antimalarial therapies[8][2][4]. The protein is homologous to mammalian P-glycoprotein, a well-known model for multidrug resistance in cancer. Mutation-specific and copy number–dependent modulation of PfMDR1 affects clinical outcomes, making it both a marker of drug resistance and a target for overcoming treatment failure in malaria[1][2][8]. The native physiological substrate of PfMDR1 is unknown, but its essentiality for parasite survival is strongly suggested. The structure of PfMDR1 includes unique regulatory features distinguishing it from other ABC transporters, and it is a primary contributor to the complex landscape of antimalarial resistance dynamics[1][3][2][7].

Other names

P-glycoprotein homologue 1Pgh1pfmdr1 (gene)

Drugs interact as substrates or inhibitors of PfMDR1, altering drug accumulation within the parasite’s digestive vacuole and thereby affecting antimalarial efficacy and resistance[2][3][4][7]. Polymorphisms and copy number alterations in pfmdr1 modulate the resistance of Plasmodium falciparum to various antimalarials by changing the efficiency of drug efflux from the digestive vacuole[8][1][2].