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Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion
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Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion
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Journal Article
Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion
2017
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Antimalarials - administration & dosage
/ Antimalarials - pharmacology
/ Antimalarials - therapeutic use
/ Aspartic Acid Endopeptidases - antagonists & inhibitors
/ Blood
/ Egress
/ Fever
/ Genomes
/ Malaria
/ Malaria, Falciparum - drug therapy
/ Mice
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - enzymology
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - pathogenicity
/ Protease
/ Protozoan Proteins - metabolism
/ Serine
