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

Authors
  • Brancucci, Nicolas M B1
  • Gerdt, Joseph P2
  • Wang, ChengQi3
  • De Niz, Mariana1
  • Philip, Nisha4
  • Adapa, Swamy R3
  • Zhang, Min3
  • Hitz, Eva5
  • Niederwieser, Igor5
  • Boltryk, Sylwia D5
  • Laffitte, Marie-Claude6
  • Clark, Martha A7
  • Grüring, Christof7
  • Ravel, Deepali7
  • Blancke Soares, Alexandra6
  • Demas, Allison7
  • Bopp, Selina7
  • Rubio-Ruiz, Belén8
  • Conejo-Garcia, Ana8
  • Wirth, Dyann F7
  • And 8 more
  • 1 Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK; Harvard T.H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02155, USA.
  • 2 Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, MA 02155, USA.
  • 3 Center for Global Health & Infectious Diseases Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620, USA.
  • 4 Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK; Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3FL, UK.
  • 5 Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; University of Basel, 4001 Basel, Switzerland. , (Switzerland)
  • 6 Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
  • 7 Harvard T.H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02155, USA.
  • 8 Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, University of Granada, 18010 Granada, Spain. , (Spain)
  • 9 Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Lodz, Poland. , (Poland)
  • 10 Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, MA 02155, USA. Electronic address: [email protected]
  • 11 Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK; Harvard T.H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02155, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell
Publication Date
Dec 14, 2017
Volume
171
Issue
7
Identifiers
DOI: 10.1016/j.cell.2017.10.020
PMID: 29129376
Source
Medline
Keywords
License
Unknown

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.

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