Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate
Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate
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DOI：
10.7554/elife.23217
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发表时间：
2017-03-02
期刊：
影响因子：
7.7
通讯作者：
de Koning-Ward, Tania F.
中科院分区：
文献类型：
--
作者：
Counihan, Natalie A.;Chisholm, Scott A.;de Koning-Ward, Tania F.
恶性疟原虫寄生虫是疟疾的病原体，它们会改变宿主红细胞，使其能够渗透到血浆中吸收补充营养并清除有毒废物。在这里，我们研究了棒状体蛋白 RhopH2 在疟原虫感染的红细胞中新的通透性途径 (NPP) 形成中的贡献。我们证明 RhopH2 与 RhopH1、RhopH3、红细胞细胞骨架和参与宿主细胞重塑的输出蛋白相互作用。第一周期中 RhopH2 表达的敲低会导致第二周期中必需维生素和辅因子的消耗，并减少嘧啶的从头合成。对寄生虫的生长、复制和进入第三周期的过渡也有重大影响。 RhopH2 敲低后，使用 NPP 进入红细胞的溶质摄取也会减少。这些发现为 RhopH 复合物在 NPP 活性中的贡献提供了直接的遗传支持，并强调了 NPP 对寄生虫生存的重要性。
Plasmodium falciparum parasites, the causative agents of malaria, modify their host erythrocyte to render them permeable to supplementary nutrient uptake from the plasma and for removal of toxic waste. Here we investigate the contribution of the rhoptry protein RhopH2, in the formation of new permeability pathways (NPPs) in Plasmodium -infected erythrocytes. We show RhopH2 interacts with RhopH1, RhopH3, the erythrocyte cytoskeleton and exported proteins involved in host cell remodeling. Knockdown of RhopH2 expression in cycle one leads to a depletion of essential vitamins and cofactors and decreased de novo synthesis of pyrimidines in cycle two. There is also a significant impact on parasite growth, replication and transition into cycle three. The uptake of solutes that use NPPs to enter erythrocytes is also reduced upon RhopH2 knockdown. These findings provide direct genetic support for the contribution of the RhopH complex in NPP activity and highlight the importance of NPPs to parasite survival.