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Role of amylopectin synthesis in Toxoplasma gondii and its implication in vaccine development against toxoplasmosis
Open Biology ( IF 4.5 ) Pub Date : 2021-06-16 , DOI: 10.1098/rsob.200384
Congcong Lyu 1, 2 , Xuke Yang 1, 2 , Jichao Yang 1, 2 , Lun Hou 1, 2 , Yanqin Zhou 1, 2 , Junlong Zhao 1, 2, 3 , Bang Shen 1, 2
Affiliation  

Toxoplasma gondii 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 T. gondii. Genetic ablation of SS abolished amylopectin production, reduced tachyzoite proliferation, and impaired the recrudescence of bradyzoites to tachyzoites. Disruption of the parasite Ca2+-dependent protein kinase 2 (CDPK2) was previously shown to cause massive amylopectin accumulation and bradyzoite death. Therefore, the Δcdpk2 mutant is thought to be a vaccine candidate. Notably, deleting SS in a Δcdpk2 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 Toxoplasma. Not least, our data underscore a potential drawback of the Δcdpk2 mutant as a vaccine candidate as it may regain full virulence by mutating amylopectin synthesis genes like SS.



中文翻译:

支链淀粉合成在弓形虫中的作用及其在弓形虫病疫苗开发中的意义

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。很大一部分弓形虫病病例是由现有慢性感染的重新激活引起的。慢性感染期间包囊的缓殖子会积累高水平的支链淀粉,而这种支链淀粉几乎不存在于快速复制的速殖子中。然而,支链淀粉的生理意义尚不完全清楚。在这里,我们确定了弓形虫中支链淀粉合成所需的淀粉合酶 (SS) 。SS 的基因消融消除了支链淀粉的产生,减少了速殖子增殖,并削弱了缓殖子向速殖子的复发。破坏寄生虫 Ca 2+依赖性蛋白激酶 2 (CDPK2) 先前已被证明会导致大量支链淀粉积累和缓殖子死亡。因此,Δcdpk2突变体被认为是候选疫苗。值得注意的是,删除Δcdpk2突变体中的 SS完全消除了淀粉积累并恢复了囊肿形成以及小鼠的毒力。这些结果共同表明,受调节的支链淀粉生产对于弓形虫的最佳生长、发育和毒力至关重要。尤其重要的是,我们的数据强调了Δcdpk2突变体作为候选疫苗的潜在缺点,因为它可能通过突变支链淀粉合成基因(如 SS)来重新获得完全的毒力。

更新日期:2021-06-16
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