Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion
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Author(s)
Nasamu, Armiyaw S.
Glushakova, Svetlana
Russo, Ilaria
Vaupel, Barbara
Oksman, Anna
Kim, Arthur S.
Fremont, Daved H.
Tolia, Niraj
Beck, Josh R.
Meyers, Marvin J.
Date Issued
October 2017
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Nasamu, Armiyaw S. et al. “Plasmepsins IX and X Are Essential and Druggable Mediators of Malaria Parasite Egress and Invasion.” Science 358, 6362 (October 2017): 518–522 © 2017 The Authors
Version
Author's final manuscript
Abstract
Proteases of the malaria parasite Plasmodium falciparum have long been investigated as drug targets. The P. falciparum genome encodes 10 aspartic proteases called plasmepsins, which are involved in diverse cellular processes. Most have been studied extensively but the functions of plasmepsins IX and X (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is essential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. We have identified compounds with potent antimalarial activity targeting PMX, including a compound known to have oral efficacy in a mouse model of malaria.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAN1478
