Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning, China.
Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, China.
mBio. 2024 Oct 16;15(10):e0133624. doi: 10.1128/mbio.01336-24. Epub 2024 Aug 29.
is an intracellular parasitic protozoan that poses a significant risk to the fetus carried by a pregnant woman or to immunocompromised individuals. tachyzoites duplicate rapidly in host cells during acute infection through endodyogeny. This highly regulated division process is accompanied by complex gene regulation networks. TgAP2XII-9 is a cell cycle-regulated transcription factor, but its specific role in the parasite cell cycle is not fully understood. In this study, we demonstrate that TgAP2XII-9 is identified as a nuclear transcription factor and is dominantly expressed during the S/M phase of the tachyzoite cell cycle. Cleavage Under Targets and Tagmentation (CUT&Tag) results indicate that TgAP2XII-9 targets key genes for the moving junction machinery (RON2, 4, and 8) and daughter cell inner membrane complex (IMC). TgAP2XII-9 deficiency resulted in a significant downregulation of rhoptry proteins and rhoptry neck proteins, leading to a severe defect in the invasion and egress efficiency of tachyzoites. Additionally, the loss of TgAP2XII-9 correlated with a substantial downregulation of multiple IMC and apicoplast proteins, leading to disorders of daughter bud formation and apicoplast inheritance and further contributing to the inability of cell division and intracellular proliferation. Our study reveals that TgAP2XII-9 acts as a critical S/M-phase regulator that orchestrates the endodyogeny and apicoplast division in tachyzoites. This study contributes to a broader understanding of the complexity of the parasite's cell cycle and its key regulators.
The intracellular apicoplast parasite poses a great threat to the public health. The acute infection of tachyzoites relies on efficient invasion by forming a moving junction structure and also fast replication by highly regulated endodyogeny. This study shows that an ApiAP2 transcription factor, TgAP2XII-9, acts as an activator for the S/M-phase gene expression, including genes related to daughter buds and moving junction formation. Loss of TgAP2XII-9 results in significant growth defects and disorders in endodyogeny and apicoplast inheritance of the parasites. Our results provide valuable insights into the transcriptional regulation of the parasite cell cycle and invading machinery in .
是一种细胞内寄生的原生动物，对孕妇携带的胎儿或免疫功能低下的个体构成重大风险。速殖子在急性感染期间通过内有丝分裂在宿主细胞中迅速复制。这个高度调控的分裂过程伴随着复杂的基因调控网络。TgAP2XII-9 是一个细胞周期调控转录因子，但它在寄生虫细胞周期中的具体作用尚不完全清楚。在这项研究中，我们证明 TgAP2XII-9 被鉴定为核转录因子，在速殖子细胞周期的 S/M 期表达占主导地位。靶向切割和标签化（CUT&Tag）结果表明，TgAP2XII-9 靶向关键基因的运动连接机制（RON2、4 和 8）和子细胞内膜复合物（IMC）。TgAP2XII-9 缺陷导致 rhoptry 蛋白和 rhoptry neck 蛋白的显著下调，导致速殖子的入侵和出芽效率严重缺陷。此外，TgAP2XII-9 的缺失与多个 IMC 和质体蛋白的大量下调相关，导致子芽形成和质体遗传的紊乱，并进一步导致细胞分裂和细胞内增殖的能力丧失。我们的研究表明，TgAP2XII-9 作为一个关键的 S/M 期调控因子，协调了 内有丝分裂和质体分裂。这项研究有助于更全面地了解寄生虫细胞周期的复杂性及其关键调控因子。
细胞内寄生的 对公共健康构成巨大威胁。速殖子的急性感染依赖于通过形成移动连接结构的有效入侵，以及通过高度调控的内有丝分裂的快速复制。这项研究表明，一种 ApiAP2 转录因子 TgAP2XII-9，作为 S/M 期基因表达的激活剂，包括与子芽和移动连接形成相关的基因。TgAP2XII-9 的缺失导致寄生虫的内有丝分裂和质体遗传的显著生长缺陷和紊乱。我们的研究结果为寄生虫细胞周期和入侵机制的转录调控提供了有价值的见解。
