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

Brancucci, Nicolas M. B. and Gerdt, Joseph P. and Wang, ChengQi and De Niz, Mariana and Philip, Nisha and Adapa, Swamy R. and Zhang, Min and Hitz, Eva and Niederwieser, Igor and Boltryk, Sylwia D. and Laffitte, Marie-Claude and Clark, Martha A. and Grüring, Christof and Ravel, Deepali and Blancke Soares, Alexandra and Demas, Allison and Bopp, Selina and Rubio-Ruiz, Belén and Conejo-Garcia, Ana and Wirth, Dyann F. and Gendaszewska-Darmach, Edyta and Duraisingh, Manoj T. and Adams, John H. and Voss, Till S. and Waters, Andrew P. and Jiang, Rays H. Y. and Clardy, Jon and Marti, Matthias. (2017) Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell, 171 (7). 1532-1544.e15.

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Official URL: http://edoc.unibas.ch/58324/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Hitz, Eva and Niederwieser, Igor and Boltryk, Sylwia Dorota and Voss, Till S
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:02 Feb 2018 10:06
Deposited On:02 Feb 2018 10:06

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