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.

中文翻译：

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溶血磷脂酰胆碱调节人类疟疾寄生虫恶性疟原虫的性阶段分化。

传播是疟原虫生命周期中的人口瓶颈，也是持续努力根除疟疾的关键干预目标。性别分化对于这一过程至关重要，因为只有称为配子体的性寄生虫才会感染蚊子媒介。配子体的产生率因环境条件而异，但外部刺激仍然模糊不清。在这里，我们表明宿主衍生的脂质溶血磷脂酰胆碱 (LysoPC) 通过抑制寄生虫性分化来控制恶性疟原虫细胞的命运。我们证明外源性 LysoPC 驱动必需的膜成分磷脂酰胆碱的生物合成。LysoPC 限制诱导补偿反应，将寄生虫代谢与性阶段特异性转录和配子体形成的激活联系起来。我们的研究结果表明，疟疾寄生虫可以感知和处理宿主衍生的生理信号以调节分化。这些数据弥补了寄生虫生物学中的一个关键知识缺口，并介绍了疟原虫性分化途径的一个主要组成部分，这可能为阻断疟疾传播提供新方法。