An essential role of the basal body protein SAS-6 in Plasmodium male gamete development and malaria transmission
Version of Record online: 24 SEP 2014
© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 17, Issue 2, pages 191–206, February 2015
How to Cite
Marques, S. R., Ramakrishnan, C., Carzaniga, R., Blagborough, A. M., Delves, M. J., Talman, A. M. and Sinden, R. E. (2015), An essential role of the basal body protein SAS-6 in Plasmodium male gamete development and malaria transmission. Cellular Microbiology, 17: 191–206. doi: 10.1111/cmi.12355
- Issue online: 22 JAN 2015
- Version of Record online: 24 SEP 2014
- Accepted manuscript online: 25 AUG 2014 11:09PM EST
- Manuscript Accepted: 19 AUG 2014
- Manuscript Revised: 11 JUL 2014
- Manuscript Received: 15 MAR 2014
- Bill and Melinda Gates Foundation
- Medicines for Malaria Venture
- Wellcome Trust
- Biotechnology and Biosciences Research Council
- Evimalar and TransMalariaBloc programs
Gametocytes are the sole Plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. Flagellum assembly of the Plasmodium 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 Plasmodium, we hypothesized that SAS-6 disruption may cause gametogenesis defects and perturb transmission. We show that Plasmodium berghei sas6 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 Pbsas6 knockouts less infectious to mosquitoes. Additionally, we show that lack of Pbsas6 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.