Plasmodium 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 PKAc by disrupting the gene in Plasmodium berghei 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 P. berghei.

中文翻译：

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伯氏疟原虫的促红细胞生成阶段不需要PKAc。

疟原虫子孢子侵入肝细胞以在哺乳动物宿主中引发感染。在受感染的肝细胞中，子孢子迅速膨胀和分化，导致成千上万的侵入性裂殖子形成并释放到血液中。子孢子和裂殖子都通过激活信号级联反应，然后释放微量微粒而侵入其宿主细胞。cAMP依赖性蛋白激酶催化亚基（PKAc）介导的信号在裂殖子侵袭红细胞中起重要作用，但其在寄生虫其他阶段的作用仍然未知。由于PKAc在血液阶段的必要性，我们通过破坏伯氏疟原虫中的基因来生成PKAc的条件突变体子孢子。突变的唾液腺子孢子能够滑行，侵袭肝细胞，并成熟成肝裂殖子，这些子裂殖子成功地从粒体中释放出来，但是当接种到小鼠中时却未能引发血液感染。我们的结果表明，疟疾寄生虫在没有PKAc的情况下完成了促红细胞生成前阶段的发展，从而增加了PKAc独立信号在伯氏疟原虫的促红细胞生成阶段中起作用的可能性。