Tachibana Mayumi, Ishino Tomoko, Takashima Eizo, Tsuboi Takafumi, Torii Motomi
Division of Molecular Parasitology, Proteo-Science Center, Ehime University, Toon, Ehime, Japan.
Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
Cell Microbiol. 2018 May;20(5):e12821. doi: 10.1111/cmi.12821. Epub 2018 Jan 23.
Anopheles mosquitoes transmit Plasmodium parasites of mammals, including the species that cause malaria in humans. Malaria pathology is caused by rapid multiplication of parasites in asexual intraerythrocytic cycles. Sexual stage parasites are also produced during the intraerythrocytic cycle and are ingested by the mosquito, initiating gametogenesis and subsequent sporogonic stage development. Here, we present a Plasmodium protein, termed microgamete surface protein (MiGS), which has an important role in male gametocyte osmiophilic body (MOB) formation and microgamete function. MiGS is expressed exclusively in male gametocytes and microgametes, in which MiGS localises to the MOB and microgamete surface. Targeted gene disruption of MiGS in a rodent malaria parasite Plasmodium yoelii 17XNL generated knockout parasites (ΔPyMiGS) that proliferate normally in erythrocytes and form male and female gametocytes. The number of MOB in male gametocyte cytoplasm is markedly reduced and the exflagellation of microgametes is impaired in ΔPyMiGS. In addition, anti-PyMiGS antibody severely blocked the parasite development in the Anopheles stephensi mosquito. MiGS might thus be a potential novel transmission-blocking vaccine target candidate.
按蚊传播哺乳动物的疟原虫,包括导致人类疟疾的疟原虫种类。疟疾病理是由寄生虫在无性红细胞内周期中的快速增殖引起的。有性阶段的寄生虫也在红细胞内周期中产生,并被蚊子摄取,从而启动配子发生和随后的孢子生殖阶段发育。在此,我们展示了一种疟原虫蛋白,称为小配子表面蛋白(MiGS),它在雄配子体嗜锇小体(MOB)形成和小配子功能中起重要作用。MiGS仅在雄配子体和小配子中表达,在其中MiGS定位于MOB和小配子表面。在啮齿动物疟原虫约氏疟原虫17XNL中对MiGS进行靶向基因破坏产生了基因敲除寄生虫(ΔPyMiGS),其在红细胞中正常增殖并形成雄配子体和雌配子体。在ΔPyMiGS中,雄配子体细胞质中MOB的数量明显减少,小配子的出丝受到损害。此外,抗PyMiGS抗体严重阻断了疟原虫在斯氏按蚊中的发育。因此,MiGS可能是一种潜在的新型传播阻断疫苗靶点候选物。