An essential role of the basal body protein SAS‐6 in Plasmodium male gamete development and malaria transmission. (24th September 2014)

• Record Type: Journal Article
• Authors: Marques, Sara R.; Ramakrishnan, Chandra; Carzaniga, Raffaella; Blagborough, Andrew M.; Delves, Michael J.; Talman, Arthur M.; Sinden, Robert E.
• Is Part Of: Cellular microbiology. Volume 17:Number 2(2015:Feb.)
• Page Start: 191
• Page End: 206
• Publication Date: 2014-09-24
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12355
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Gametocytes are the sole <italic>P</italic><italic>lasmodium</italic> parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. Flagellum assembly of the <italic>P</italic><italic>lasmodium</italic> male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. The centriole/basal body protein SAS‐6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ciliary abnormalities in a diverse array of eukaryotes. Since basal body and flagellum assembly are intimately coupled to male gamete development in <italic>P</italic><italic>lasmodium</italic>, we hypothesized that SAS‐6 disruption may cause gametogenesis defects and perturb transmission. We show that <italic>P</italic><italic>lasmodium berghei</italic> <italic>sas6</italic> knockouts display severely abnormal male gametogenesis presenting reduced basal body numbers, axonemal assembly defects and abnormal nuclear allocation. The defects in gametogenesis reduce fertilization and render <italic>Pbsas6</italic> knockouts less infectious to mosquitoes. Additionally, we show that lack of <italic>Pbsas6</italic> blocks transmission from mosquito to vertebrate host, revealing an additional yet undefined role in ookinete to sporulating oocysts transition. These findings underscore the vulnerability of the basal body/SAS‐6 to malaria transmission blocking interventions.</p> </abstract>