Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane

In the plasmoDB database, 16 members of the P. falciparum ABC family can be identified, 11 of which are putative transport proteins. A phylogenetic analysis of the aligned NBDs of the PfABC genes was performed. Antibodies against PfMRP1 (PfABCC1), PfMRP2 (PfABCC2), and PfMDR5 (PfABCB5) were generated, affinity purified and used in immunocytochemistry to localize the proteins in the asexual stages of the parasite.The ABC family members of P. falciparum were categorized into subfamilies. The ABC B subfamily was the largest and contained seven members. Other family members that could be involved in drug transport are PfABCC1, PfABCC2, PfABCG1, and PfABCI3. The expression and localization of three ABC transport proteins was determined. PfMRP1, PfMRP2, and PfMDR5 are localized to the plasma membrane in all asexual stages of the parasite.In conclusion, 11 of the 16 ABC proteins in the P. falciparum genome are putative transport proteins, some of which might be involved in drug resistance. Moreover, it was demonstrated that three of these proteins are expressed on the parasite's plasma membrane.Drug resistance is a major problem in malaria. Today only a limited number of effective anti-malarials is available. An important reason for therapeutic failure in malaria treatment could be that drugs do not reach their target sites, due to active extrusion by the parasite. The transport proteins responsible for this type of resistance are so-called multidrug resistance proteins (MDR/MRP), most of which belong to the superfamily of ATP binding cassette (ABC) proteins, one of the largest protein families. Many of these plasma membrane proteins actively pump out a wide range of structurally and functionally diverse amphipathic drugs, thereby decreasing the intracellular drug accumulation and resulting in drug resistance [1,2]. The structure of a typical ABC transporter consists of six trans-membrane segments that form a trans-membrane domain (TMD) and the Walker A and Walker B motifs