Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29074774.
- Also identified by DOI 10.1126/science.aan1478 and PMC identifier 5928414.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Proteases of the malaria parasite <i>Plasmodium falciparum</i> have long been investigated as drug targets. The <i>P. falciparum</i> 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.
Medical subject headings
- Antimalarials
- Aspartic Acid Endopeptidases
- Malaria, Falciparum
- Plasmodium falciparum