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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Functional redundancy of three mitochondrial Mg2+/Mn2+-dependent protein phosphatases (PPMs) in Toxoplasma gondii

Abstract: Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.

Key words: Toxoplasma gondii; Mitochondria; PPMs; Functional redundancy; Proliferation

Chinese Summary  <2> 刚地弓形虫三种线粒体Mg2+/Mn2+依赖性蛋白磷酸酶(PPMs)存在功能冗余

盛楷茵1,2,陈学秋1,阳毅敏1,夏洁1,宋凯悦1,Chaoqun YAO3,杨怡1,杜爱芳1,马光旭1,2
1浙江大学动物科学学院动物预防医学研究所,中国杭州市,310058
2浙江大学-新昌联合创新中心(天姥实验室),高创科技园区,中国新昌市,312500
3罗斯大学兽医学院, 生物医学部人畜共患病和热带传染病卫生中心,巴斯特尔,圣基茨和尼维斯,KN-0101
摘要:弓形虫(Toxoplasma gondii)是一种专性胞内寄生的顶复门原虫,可以感染包括人在内的几乎所有温血动物,引起全球性的人畜共患弓形虫病,从而危害人类健康和畜牧业发展,并造成经济损失。刚地弓形虫独特的线粒体是弓形虫病防控的理想靶细胞器。线粒体中的Mg2+/Mn2+依赖性蛋白磷酸酶(PPMs)在细胞生长、能量代谢和环境应激中发挥着重要的作用。然而,人们对弓形虫的线粒体PPMs知之甚少。在本研究中,我们鉴定出三种PPMs,即TgPPM8(TGGT1_218590)、TgPPM10(TGGT1_254410)和TgPPM19(TGGT1_275840),均定位于弓形虫速殖子的线粒体基质中。这三个PPMs中任一PPM编码基因的缺失(Δppm8、Δppm10或Δppm19)均会导致弓形虫速殖子生长抑制与增殖能力减弱,以及另外两个PPMs编码基因信使RNA(mRNA)水平的升高,但不影响弓形虫速殖子在小鼠体内的毒力。Δppm8Δppm10或Δppm8Δppm19双重缺失可显著导致弓形虫速殖子体外生长抑制与增殖减缓。由于潜在的突变致死效应,本研究未获得Δppm10Δppm19和Δppm8Δppm10Δppm19缺失虫株。上述结果表明,弓形虫线粒体PPMs间存在功能冗余,是弓形虫线粒体生物学研究的新发现,为具有重要兽医和医学意义的弓形虫的防控靶点的发掘提供了新思路。

关键词组:刚地弓形虫;线粒体;Mg2+/Mn2+依赖性蛋白磷酸酶(PPMs);功能冗余;增殖


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DOI:

10.1631/jzus.B2400308

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On-line Access:

2025-04-23

Received:

2024-06-18

Revision Accepted:

2024-09-06

Crosschecked:

2025-04-24

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