The Plasmodium falciparum protein PfMRP1 functions as an influx ABC transporter

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play an important role in mediating solute or drug transport across cellular membranes. Although this class of transporters has been well characterized in diverse organisms little is known about the physiological roles in Plasmodium falciparum, the deadliest malaria parasite species. We studied the Plasmodium falciparum Multidrug Resistance-associated Protein 1 (PfMRP1; PF3D7_0112200), an ABC transporter localized to the parasite plasma membrane, generating genetic disrupted parasites. We demonstrate that parasites with disrupted pfmrp1 are resistant to folate analogs, methotrexate and aminopterin, with antimalarial activity. This phenotype occurs due to reduction in compound accumulation in the parasite cytoplasm. Phylogenetic analysis supports pfmrp1 being distantly related to ABC transporters in other eukaryotes, suggesting an unusual function. We propose that PfMRP1 can act as a solute importer, a function not previously observed in this organism.