Open AccessMultidrug ATP‐binding cassette transporters are essential for hepatic development of Plasmodium sporozoites
Author(s) -
Rijpma Sanna R.,
Velden Maarten,
GonzálezPons Maria,
Annoura Takeshi,
Schaijk Ben C. L.,
Gemert GeertJan,
Heuvel Jeroen J. M. W.,
Ramesar Jai,
ChevalleyMaurel Severine,
Ploemen Ivo H.,
Khan Shahid M.,
Franetich JeanFrancois,
Mazier Dominique,
Wilt Johannes H.W.,
Serrano Adelfa E.,
Russel Frans G. M.,
Janse Chris J.,
Sauerwein Robert W.,
Koenderink Jan B.,
FrankeFayard Blandine M.
Publication year - 2016
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12517
Subject(s) - biology , plasmodium berghei , atp binding cassette transporter , plasmodium falciparum , multidrug resistance associated protein 2 , multidrug resistance associated proteins , mutant , transporter , plasmodium (life cycle) , malaria , parasite hosting , biochemistry , gene , immunology , world wide web , computer science
Summary Multidrug resistance‐associated proteins (MRPs) belong to the C‐family of ATP‐binding cassette (ABC) transport proteins and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. Rodent malaria parasites encode a single ABC transporter subfamily C protein, whereas human parasites encode two: MRP1 and MRP2. Although associated with drug resistance, their biological function and substrates remain unknown. To elucidate the role of MRP throughout the parasite life cycle, Plasmodium berghei and Plasmodium falciparum mutants lacking MRP expression were generated. P . berghei mutants lacking expression of the single MRP as well as P . falciparum mutants lacking MRP1, MRP2 or both proteins have similar blood stage growth kinetics and drug‐sensitivity profiles as wild type parasites. We show that MRP1‐deficient parasites readily invade primary human hepatocytes and develop into mature liver stages. In contrast, both P . falciparum MRP2‐deficient parasites and P . berghei mutants lacking MRP protein expression abort in mid to late liver stage development, failing to produce mature liver stages. The combined P . berghei and P . falciparum data are the first demonstration of a critical role of an ABC transporter during Plasmodium liver stage development.