Huang Wanyi, He Wei, Huang Yue, Tang Yongping, Chen Ming, Sun Lianbei, Yang Zuwei, Hou Tianyi, Liu Huimin, Chen Haoyu, Wang Tianpeng, Li Na, Guo Yaqiong, Xiao Lihua, Feng Yaoyu
State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Nat Commun. 2024 Dec 30;15(1):10774. doi: 10.1038/s41467-024-54995-4.
The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C. hominis isolates and generate a new IbA12G3 genome at the chromosome level. Comparative analysis with 222 human isolates shows significant genetic divergence of the animal isolates, with genetic recombination among them. They have additional subtelomeric insulinase and MEDLE genes. In interferon-γ knockout mice, three monkey isolates show differences in infectivity and induce higher and longer oocyst shedding than a reference C. parvum isolate. Deletion of the MEDLE genes significantly reduces the growth and pathogenicity of a virulent strain in mice. Co-infection of two fluorescence-tagged C. hominis subtypes produces bicolored oocysts, supporting the conclusion that mixed subtype infections can lead to genetic recombination. These data provide insight into potential determinants of host infectivity in Cryptosporidium, and a convenient animal model for biological studies of C. hominis.
人兽共患的微小隐孢子虫（Cryptosporidium hominis）与动物源性的微小隐孢子虫（C. parvum）不同，它对动物没有感染性，但最近在非人灵长类动物和马中发现了几种不同的亚型。在这里，我们对17株动物微小隐孢子虫分离株进行了测序，并在染色体水平上生成了一个新的IbA12G3基因组。与222株人类分离株的比较分析表明，动物分离株存在显著的遗传差异，并且它们之间存在基因重组。它们还具有额外的端粒旁胰岛素酶和MEDLE基因。在干扰素-γ基因敲除小鼠中，三株猴子分离株在感染性方面表现出差异，并且比参考微小隐孢子虫分离株诱导更高和更长时间的卵囊排出。删除MEDLE基因显著降低了毒力菌株在小鼠中的生长和致病性。两种荧光标记的微小隐孢子虫亚型的共感染产生了双色卵囊，支持了混合亚型感染可导致基因重组的结论。这些数据为微小隐孢子虫宿主感染性的潜在决定因素提供了见解，并为微小隐孢子虫的生物学研究提供了一个方便的动物模型。
