State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Key Laboratory of Preventive Medicine in Hubei Province, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Open Biol. 2021 Jun;11(6):200384. doi: 10.1098/rsob.200384. Epub 2021 Jun 16.
is a ubiquitous pathogen infecting one-third of the global population. A significant fraction of toxoplasmosis cases is caused by reactivation of existing chronic infections. The encysted bradyzoites during chronic infection accumulate high levels of amylopectin that is barely present in fast-replicating tachyzoites. However, the physiological significance of amylopectin is not fully understood. Here, we identified a starch synthase (SS) that is required for amylopectin synthesis in . Genetic ablation of SS abolished amylopectin production, reduced tachyzoite proliferation, and impaired the recrudescence of bradyzoites to tachyzoites. Disruption of the parasite Ca-dependent protein kinase 2 (CDPK2) was previously shown to cause massive amylopectin accumulation and bradyzoite death. Therefore, the mutant is thought to be a vaccine candidate. Notably, deleting SS in a mutant completely abolished starch accrual and restored cyst formation as well as virulence in mice. Together these results suggest that regulated amylopectin production is critical for the optimal growth, development and virulence of . Not least, our data underscore a potential drawback of the mutant as a vaccine candidate as it may regain full virulence by mutating amylopectin synthesis genes like SS.
刚地弓形虫是一种普遍存在的病原体，感染了全球三分之一的人口。相当一部分弓形虫病是由现有慢性感染的再激活引起的。在慢性感染中，囊包的缓殖子积累了大量的支链淀粉，而在快速复制的速殖子中几乎不存在支链淀粉。然而，支链淀粉的生理意义尚未完全理解。在这里，我们鉴定了一种淀粉合酶（SS），它是刚地弓形虫中支链淀粉合成所必需的。SS 的基因缺失导致支链淀粉的产生减少，速殖子的增殖减少，并损害了缓殖子向速殖子的复燃。先前已经证明，破坏寄生虫 Ca 依赖性蛋白激酶 2（CDPK2）会导致大量支链淀粉积累和缓殖子死亡。因此，该突变体被认为是一种疫苗候选物。值得注意的是，在一个 突变体中删除 SS 完全消除了淀粉的积累，并恢复了囊泡的形成以及在小鼠中的毒力。这些结果表明，支链淀粉的调节产生对于刚地弓形虫的最佳生长、发育和毒力至关重要。最重要的是，我们的数据强调了作为疫苗候选物的 突变体的一个潜在缺陷，因为它可能通过突变像 SS 这样的支链淀粉合成基因而重新获得完全的毒力。
