Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host
Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host
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DOI：
10.1128/mcb.00553-08
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发表时间：
2008-10-01
影响因子：
5.3
通讯作者：
Kappe, Stefan H. I.
中科院分区：
文献类型：
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作者：
Mikolajczak, Sebastian A.;Silva-Rivera, Hilda;Kappe, Stefan H. I.
疟疾寄生虫子孢子传播阶段在按蚊中肠上的寄生虫卵囊内发育和分化。成功地将寄生虫接种到哺乳动物宿主中关键取决于子孢子首先感染蚊子唾液腺的能力。当子孢子从中肠卵囊转移到唾液腺时，观察到组织感染能力的显著变化。我们的微阵列分析显示，与卵囊子孢子相比，唾液腺子孢子上调至少124个独特基因的表达。相反，卵囊子孢子在感染唾液腺之前显示至少47个基因的上调（在卵囊子孢子中上调[UOS基因]）。UOS 3的靶向基因缺失，编码一个假定的跨膜蛋白，具有定位于子孢子分泌细胞器的血小板反应蛋白重复序列，使卵囊子孢子不能感染蚊子唾液腺，但保持了寄生虫的肝脏感染能力。这种表型证明了UOS差异表达的重要性。因此，UIS-UOS基因分类提供了一个框架，以阐明疟原虫子孢子的感染性和传播成功的全基因组规模。本文鉴定的基因可能代表基于载体的传播阻断策略（UOS基因）以及预防哺乳动物宿主感染的策略（UIS基因）的靶标。
The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes).