Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites

Cellular Microbiology
Sanna R RijpmaBlandine M D Franke-Fayard

Abstract

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 o...Continue Reading

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Citations

Jun 1, 2016·Scientific Reports·Hirdesh KumarFriedrich Frischknecht
Jun 15, 2016·The American Journal of Tropical Medicine and Hygiene·Maarten van der VeldenJan B Koenderink
Mar 1, 2017·Cold Spring Harbor Perspectives in Medicine·Ashley M Vaughan, Stefan H I Kappe
Nov 9, 2019·Biological Reviews of the Cambridge Philosophical Society·Rowena E Martin

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