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

Nicolas M.B. Brancucci, Joseph P. Gerdt, Cheng Qi 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. WirthEdyta Gendaszewska-Darmach, Manoj T. Duraisingh, John H. Adams, Till S. Voss, Andrew P. Waters, Rays H.Y. Jiang, Jon Clardy*, Matthias Marti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

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. The host-derived lipid lysophosphatidylcholine controls Plasmodium falciparum cell fate by repressing parasite sexual differentiation, a key step in malaria transmission.

Original languageEnglish (US)
Pages (from-to)1532-1544.e15
JournalCell
Volume171
Issue number7
DOIs
StatePublished - Dec 14 2017

Keywords

  • Kennedy pathway
  • Plasmodium falciparum
  • environmental sensing
  • lysophosphatidylcholine
  • malaria
  • phospholipid metabolism
  • sexual differentiation
  • transmission

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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