Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co‐factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium. Here, we report on the expression, subcellular localisation and function of the parasite's folate transporter 2 (FT2) during life cycle progression in the murine malaria parasite Plasmodium berghei. Using live fluorescence microscopy of genetically engineered parasites, we demonstrate that FT2 localises to the apicoplast. In invasive P. berghei stages, a fraction of FT2 is also observed at the apical end. Upon genetic disruption of FT2, blood and liver infection, gametocyte production and mosquito colonisation remain unaltered. But in the Anopheles vector, FT2‐deficient parasites develop inflated oocysts with unusual pulp formation consisting of numerous single‐membrane vesicles, which ultimately fuse to form large cavities. Ultrastructural analysis suggests that this defect reflects aberrant sporoblast formation caused by abnormal vesicular traffic. Complete sporogony in FT2‐deficient oocysts is very rare, and mutant sporozoites fail to establish hepatocyte infection, resulting in a complete block of parasite transmission. Our findings reveal a previously unrecognised organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector.

中文翻译：

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顶质体叶酸转运蛋白对于疟疾寄生虫的孢子生殖至关重要。


疟疾寄生虫是快速复制的单细胞生物，需要大量的叶酸来合成 DNA。尽管这种关键辅助因子对于寄生虫的生存起着核心作用，但人们对疟原虫体内寄生叶酸的运输知之甚少。在这里，我们报告了鼠疟原虫伯氏疟原虫生命周期进展过程中寄生虫叶酸转运蛋白 2 (FT2) 的表达、亚细胞定位和功能。使用基因工程寄生虫的活体荧光显微镜，我们证明 FT2 定位于顶质体。在伯氏疟原虫侵入阶段，在顶端也观察到一小部分 FT2。 FT2基因遭到破坏后，血液和肝脏感染、配子体产生和蚊子定植保持不变。但在按蚊载体中，缺乏FT2 的寄生虫会发育出膨胀的卵囊，并形成不寻常的果肉，由大量单膜囊泡组成，最终融合形成大空腔。超微结构分析表明，这种缺陷反映了由异常的囊泡交通引起的异常孢子母细胞形成。 FT2缺陷的卵囊中完整的孢子形成非常罕见，突变的子孢子无法建立肝细胞感染，从而导致寄生虫传播的完全阻断。我们的研究结果揭示了一种以前未被识别的细胞器叶酸转运蛋白，它对节肢动物载体中的病原体成熟发挥着关键作用。