Journal
CELLULAR MICROBIOLOGY
Volume 18, Issue 3, Pages 369-383Publisher
WILEY
DOI: 10.1111/cmi.12517
Keywords
-
Categories
Funding
- Radboud University Medical Centre
- UPR-NIH-MBRS/RISE [R25GM061838]
- NIH [S06GM008224, G12-MD 007600, 5 T37 MD001477-08]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available