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dc.contributor.authorJennison, Charlie
dc.contributor.authorLucantoni, Leonardo
dc.contributor.authorO'Neill, Matthew T
dc.contributor.authorMcConville, Robyn
dc.contributor.authorErickson, Sara M
dc.contributor.authorCowman, Alan F
dc.contributor.authorSleebs, Brad E
dc.contributor.authorAvery, Vicky M
dc.contributor.authorBoddey, Justin A
dc.date.accessioned2020-03-31T01:19:27Z
dc.date.available2020-03-31T01:19:27Z
dc.date.issued2019
dc.identifier.issn2211-1247
dc.identifier.doi10.1016/j.celrep.2019.11.073
dc.identifier.urihttp://hdl.handle.net/10072/392789
dc.description.abstractPlasmodium 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherCell Press
dc.relation.ispartofpagefrom3796
dc.relation.ispartofpageto+
dc.relation.ispartofissue12
dc.relation.ispartofjournalCell Reports
dc.relation.ispartofvolume29
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1116
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsCell Biology
dc.subject.keywordsMALARIA PARASITE
dc.subject.keywordsPROTEIN EXPORT
dc.titleInhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationJennison, C; Lucantoni, L; O'Neill, MT; McConville, R; Erickson, SM; Cowman, AF; Sleebs, BE; Avery, VM; Boddey, JA, Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes, Cell Reports, 2019, 29 (12), pp. 3796-+
dcterms.dateAccepted2019-11-15
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2020-03-31T01:14:20Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorAvery, Vicky M.
gro.griffith.authorLucantoni, Leonardo


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