Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum
Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum
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DOI：
10.1126/sciadv.aaz5057
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发表时间：
2020-06-01
期刊：
影响因子：
13.6
通讯作者：
Cortes, Alfred
中科院分区：
文献类型：
--
作者：
Llora-Batlle, Oriol;Michel-Todo, Lucas;Cortes, Alfred
疟疾的传播需要一些无性寄生虫转化为有性体，称为配子体。性发育的最初阶段，包括性行为承诺的分裂体和性环，仍然特征不佳，主要是因为它们在形态上与无性同龄人相同，而且只有一小部分寄生虫经历了性发育。在这里，我们描述了一种基于PfAP2-G转录因子的条件表达来控制人类疟疾寄生虫恶性疟原虫的性转换的系统。使用这一系统，类似于90%的寄生虫在诱导后转变为有性形式，从而能够在不进一步纯化的情况下表征承诺的和早期的有性阶段。我们在转录和表型水平上表征了性行为承诺的裂殖体和性环，这揭示了参与溶质运输的基因在性行为承诺时的下调，以及其他发现。新的诱导系将在更多的水平上促进对早期性阶段的研究，包括多组学特征和药物敏感性分析。
Malaria transmission requires that some asexual parasites convert into sexual forms termed gametocytes. The initial stages of sexual development, including sexually committed schizonts and sexual rings, remain poorly characterized, mainly because they are morphologically identical to their asexual counterparts and only a small subset of parasites undergo sexual development. Here, we describe a system for controlled sexual conversion in the human malaria parasite Plasmodium falciparum, based on conditional expression of the PfAP2-G transcription factor. Using this system, similar to 90 percent of the parasites converted into sexual forms upon induction, enabling the characterization of committed and early sexual stages without further purification. We characterized sexually committed schizonts and sexual rings at the transcriptomic and phenotypic levels, which revealed down-regulation of genes involved in solute transport upon sexual commitment, among other findings. The new inducible lines will facilitate the study of early sexual stages at additional levels, including multiomic characterization and drug susceptibility assays.