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

Brancucci, Nicolas M. B.; Gerdt, Joseph P.; Wang, Chengqi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R.; Zhang, MIN; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D.; laffitte, Marie-ClauDe; Clark, Martha A.; Gruring, Christof; Ravel, Deepali; Soares,

Publicación: CELL
VL / 171 - BP / 1532 - EP / +
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 gameto-cytes, 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.

Access level

Green accepted, Green published, Gold other