Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum Brancucci, Nicolas M.B. Rubio Ruiz, Belén Conejo García, Ana We thank C. Ben Mamoun for sharing the anti-PMT antibody and K. Dantzler for critically reading the manuscript. We are grateful to P. Lui and W. Beyer for technical assistance. This work was supported by Senior Investigator Award 172862 and IRS Award 172805 from the Wellcome Trust and a career development award from the Burroughs Wellcome Fund to M.M., NIH grants GM086258 to J.C. and R01RHL139337 to M.T.D., and a Centre Award 104111 to the Wellcome Centre for Molecular Parasitology and Swiss National Science Foundation grants (31003A_163258 and BSCGI0_157729) to T.S.V. N.M.B.B. and M.D.N. received Postdoc.Mobility fellowships from the Swiss National Science Foundation (P300PA_160975 and P2BEP3_165396, respectively). J.P.G. was supported by an 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. 2020-07-30T08:35:02Z 2020-07-30T08:35:02Z 2017-12-14 info:eu-repo/semantics/article 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] http://hdl.handle.net/10481/63200 10.1016/j.cell.2017.10.020 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Elsevier