Research

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

Reginald A Kavishe^1,3 , Jeroen MW van den Heuvel¹ , Marga van de Vegte-Bolmer² , Adrian JF Luty² , Frans GM Russel¹ and Jan B Koenderink¹

¹  Department of Pharmacology and Toxicology 149, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands

²  Department of Medical Microbiology 268, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands

³  Kilimanjaro Christian Medical College of Tumaini University, P. O. Box 2240, Moshi, Tanzania

author email corresponding author email

Malaria Journal 2009, 8:205doi:10.1186/1475-2875-8-205

Published:	28 August 2009

Abstract

Background

The spread of drug resistance has been a major obstacle to the control of malaria. The mechanisms underlying drug resistance in malaria seem to be complex and multigenic. The current literature on multiple drug resistance against anti-malarials has documented PfMDR1, an ATP-binding cassette (ABC) protein, as an important determinant of resistance. In the Plasmodium falciparum genome, there are several ABC transporters some of which could be putative drug transporting proteins. In order to understand the molecular mechanisms underlying drug resistance, characterization of these transporters is essential. The aim of this study was to characterize and localize putative ABC transporters.

Methods

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.

Results

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.

Conclusion

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.