Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India
Life Sci Alliance. 2019 May 29;2(3). doi: 10.26508/lsa.201900352. Print 2019 Jun.
sporozoites invade hepatocytes to initiate infection in the mammalian host. In the infected hepatocytes, sporozoites undergo rapid expansion and differentiation, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Both sporozoites and merozoites invade their host cells by activation of a signaling cascade followed by discharge of micronemal content. cAMP-dependent protein kinase catalytic subunit (PKAc)-mediated signaling plays an important role in merozoite invasion of erythrocytes, but its role during other stages of the parasite remains unknown. Becaused of the essentiality of PKAc in blood stages, we generated conditional mutants of by disrupting the gene in sporozoites. The mutant salivary gland sporozoites were able to glide, invaded hepatocytes, and matured into hepatic merozoites which were released successfully from merosome, however failed to initiate blood stage infection when inoculated into mice. Our results demonstrate that malaria parasite complete preerythrocytic stages development without PKAc, raising the possibility that the PKAc independent signaling operates in preerythrocytic stages of .
疟原虫的子孢子侵入肝细胞,在哺乳动物宿主体内引发感染。在受感染的肝细胞中,子孢子迅速增殖和分化,导致数千个侵袭性裂殖子形成并释放到血液中。子孢子和裂殖子通过激活信号级联反应并释放微线体内容物来侵入其宿主细胞。cAMP 依赖性蛋白激酶催化亚基(PKAc)介导的信号转导在裂殖子侵入红细胞中起着重要作用,但在寄生虫的其他阶段其作用尚不清楚。由于 PKAc 在血期的重要性,我们通过破坏 中的基因在 子孢子中产生了条件性突变体。突变的唾液腺子孢子能够滑行,侵入肝细胞,并成熟为肝裂殖子,这些裂殖子从 merosome 中成功释放,但当接种到小鼠中时未能引发血期感染。我们的结果表明,疟原虫在没有 PKAc 的情况下完成了前红细胞期的发育,这增加了 PKAc 独立信号在疟原虫前红细胞期发挥作用的可能性。