Inhibition of Plasmepsin V activity blocks Plasmodium falciparum gametocytogenesis and transmission to mosquitoes
- Author(s)
- Jennison, C; Lucantoni, L; O'Neill, MT; McConville, R; Erickson, SM; Cowman, AF; Sleebs, BE; Avery, VM; Boddey, JA;
- Details
- Publication Year 2019-12-17,Volume 29,Issue #12,Page 3796-3806 e4
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- Abstract
- Plasmodium falciparum gametocytes infect mosquitoes and are responsible for malaria transmission. New interventions that block transmission could accelerate malaria elimination. Gametocytes develop within erythrocytes and activate protein export pathways that remodel the host cell. Plasmepsin V (PMV) is an aspartyl protease that is required for protein export in asexual parasites, but its function and essentiality in gametocytes has not been definitively proven, nor has PMV been assessed as a transmission-blocking drug target. Here, we show that PMV is expressed and can be inhibited specifically in P. falciparum stage I-II gametocytes. PMV inhibitors block processing and export of gametocyte effector proteins and inhibit development of stage II-V gametocytes. Gametocytogenesis in the presence of sublethal inhibitor concentrations results in stage V gametocytes that fail to infect mosquitoes. Therefore, PMV primes gametocyte effectors for export, which is essential for the development and fitness of gametocytes for transmission to mosquitoes.
- Publisher
- Elsevier
- Research Division(s)
- Infectious Diseases And Immune Defence; Chemical Biology
- PubMed ID
- 31851913
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2019.11.073
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2019.11.073- NHMRC Grants
- NHMRC/1010326, NHMRC/1049811,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-12-20 11:13:12
Last Modified: 2019-12-20 11:16:34