Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion

Armiyaw S. Nasamu, Svetlana Glushakova, Ilaria Russo, Barbara Vaupel, Anna Oksman, Arthur S. Kim, Daved H. Fremont, Niraj Tolia, Josh R. Beck, Marvin J. Meyers, Jacquin C. Niles, Joshua Zimmerberg, Daniel E. Goldberg

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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.

Original languageEnglish
Pages (from-to)518-522
Number of pages5
JournalScience
Volume358
Issue number6362
DOIs
StatePublished - Oct 27 2017

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