Zhu Yuchao, Fan Bolin, Xu Hao, Li Yazhou, Liang Xiaohan, Xue Lilan, Wei Liting, Fan Fuqiang, Zhang Xin, Chen Yukun, Qian Shanshan, Shen Bang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province, China.
Hubei Hongshan Laboratory, Wuhan, Hubei Province, China.
Nat Commun. 2025 Jul 1;16(1):5757. doi: 10.1038/s41467-025-60795-1.
Toxoplasma gondii is an extremely successful parasite infecting one third of the human population and numerous animals. It has a complex life cycle with multiple developmental stages that are key for its transmission and pathogenesis. But how the developmental programs are regulated is largely unknown. Here, we screen putative chromatin remodeling proteins in T. gondii and find that a novel complex containing an evolutionarily conserved ATPase SNF2L is critical for programming the parasite's development. This complex contains four core proteins and conditional depletion of three of them leads to similar expression changes of developmentally regulated genes, including increased transcription of genes involved in sexual commitment and development. Accordingly, depletion of SNF2L causes merogony and out-budding types of division, which are otherwise only observed at the enteroepithelial stages within definitive hosts where sexual reproduction of the parasite occurs. After being recruited to target regions, SNF2L regulates gene expression by modulating local chromatin accessibility or by recruiting accessory proteins to its binding sites, thus ensuring that the gene expression and reproduction patterns are matched to the life cycle stages. Conditional depletion of SNF2L offers an opportunity to study the unique biology of the parasite during pre-sexual and sexual developments in vitro.
刚地弓形虫是一种极其成功的寄生虫,感染着全球三分之一的人口以及众多动物。它具有复杂的生命周期,包含多个发育阶段,这些阶段对其传播和发病机制至关重要。然而,发育程序是如何调控的,目前仍 largely 未知。在此,我们在刚地弓形虫中筛选了假定的染色质重塑蛋白,发现一个包含进化上保守的 ATP 酶 SNF2L 的新型复合物对规划寄生虫的发育至关重要。该复合物包含四个核心蛋白,其中三个的条件性缺失会导致发育调控基因出现相似的表达变化,包括参与有性生殖和发育的基因转录增加。相应地,SNF2L 的缺失会导致裂殖生殖和出芽型分裂,而这些分裂类型通常仅在终末宿主的肠上皮阶段观察到,此时寄生虫会进行有性生殖。被招募到靶区域后,SNF2L 通过调节局部染色质可及性或通过将辅助蛋白招募到其结合位点来调控基因表达,从而确保基因表达和繁殖模式与生命周期阶段相匹配。SNF2L 的条件性缺失为在体外研究寄生虫在性成熟前和性发育过程中的独特生物学特性提供了一个机会。