Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum
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Brancucci, N. M., Gerdt, J. P., Wang, C., De Niz, M., Philip, N., Adapa, S. R., ... & Laffitte, M. C. (2017). Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell, 171(7), 1532-1544. [https://doi.org/10.1016/j.cell.2017.10.020]
SponsorshipWellcome Trust 172862 172805; Burroughs Wellcome Fund; United States Department of Health & Human Services National Institutes of Health (NIH) - USA GM086258 R01RHL139337; Centre Award 104111; Swiss National Science Foundation (SNSF) 31003A_163258 BSCGI0_157729 P300PA_160975 P2BEP3_165396; NIH NRSA fellowship from the NIGMS F32 GM116205
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.