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Merck

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

Cell (2017-11-14)
Nicolas M B Brancucci, Joseph P Gerdt, ChengQi Wang, Mariana De Niz, Nisha Philip, Swamy R Adapa, Min Zhang, Eva Hitz, Igor Niederwieser, Sylwia D Boltryk, Marie-Claude Laffitte, Martha A Clark, Christof Grüring, Deepali Ravel, Alexandra Blancke Soares, Allison Demas, Selina Bopp, Belén Rubio-Ruiz, Ana Conejo-Garcia, Dyann F Wirth, Edyta Gendaszewska-Darmach, Manoj T Duraisingh, John H Adams, Till S Voss, Andrew P Waters, Rays H Y Jiang, Jon Clardy, Matthias Marti
RESUMEN

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.

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Sigma-Aldrich
Concanavalin A from Canavalia ensiformis (Jack bean), Type IV-S, lyophilized powder, aseptically processed, BioReagent, suitable for cell culture
Sigma-Aldrich
Thiazole Orange, Dye content ~90 %
Sigma-Aldrich
Choline chloride-(trimethyl-d9), 98 atom % D
Avanti
Edelfosine, Avanti Research - A Croda Brand 999995P, powder
Avanti
16:0-12:0 NBD PA, Avanti Research - A Croda Brand 810174P, powder