Lysophosphatidylcholine regulates sexual Stage differentiation in the human malaria parasite Plasmodium falciparum

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)

[img]
Preview
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, Marie-Claude and Philip, Dr Nisha and Waters, Professor Andrew and Blancke Soares, Dr Alexandra and Marti, Professor Matthias and De Niz, Dr Mariana and Brancucci, Dr Nicolas
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 > Institute of Infection Immunity and Inflammation
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN:0092-8674
ISSN (Online):1097-4172
Published Online:01 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

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
711751Elucidating mechanisms of extracellular vesiclemediated cellular communication and stage conversion in malaria parasites.Matthias MartiWellcome Trust (WELLCOTR)110166/B/15/ZIII - PARASITOLOGY
711752Elucidating mechanisms of extracellular vesiclemediated cellular communication and stage conversion in malaria parasites.Matthias MartiWellcome Trust (WELLCOTR)110166/Z/15/ZIII - PARASITOLOGY