Brancucci, N. M.B. et al. (2017) Lysophosphatidylcholine regulates sexual Stage differentiation in the human malaria parasite Plasmodium falciparum. Cell, 171(7), 1532-1544.e15. (doi: 10.1016/j.cell.2017.10.020) (PMID:29129376) (PMCID:PMC5733390)
|
Text
149981.pdf - Published Version Available under License Creative Commons Attribution. 4MB |
Abstract
Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Laffitte, Miss Marie-Claude and Philip, Dr Nisha and Waters, Professor Andy and Blancke Soares, Dr Alexandra and Marti, Professor Matthias and De Niz, Dr Mariana and Brancucci, Dr Nicolas |
| Creator Roles: | Brancucci, N. M.B.Conceptualization, Writing – original draft, Writing – review and editing Waters, A. P.Supervision Marti, M.Supervision, Writing – review and editing |
| Authors: | Brancucci, N. M.B., Gerdt, J. P., Wang, C., De Niz, M., Philip, N., Adapa, S. R., Zhang, M., Hitz, E., Niederwieser, I., Boltryk, S. D., Laffitte, M.-C., Clark, M. A., Grüring, C., Ravel, D., Blancke Soares, A., Demas, A., Bopp, S., Rubio-Ruiz, B., Conejo-Garcia, A., Wirth, D. F., Gendaszewska-Darmach, E., Duraisingh, M. T., Adams, J. H., Voss, T. S., Waters, A. P., Jiang, R. H.Y., Clardy, J., and Marti, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Cell |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 0092-8674 |
| ISSN (Online): | 1097-4172 |
| Published Online: | 09 November 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Cell 171(7):1532-1544.e15 |
| Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information