Analysis of the virulence determination mechanisms in a local Toxoplasma strain (T.gHB1) isolated from central China

Analysis of the virulence determination mechanisms in a local Toxoplasma strain (T.gHB1) isolated from central China
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华中地区弓形虫本地株(T.gHB1)毒力测定机制分析

DOI:
10.1007/s00436-016-5141-z
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发表时间:
2016-05
影响因子:
2
通讯作者:
Zhao Junlong
Zhao Junlong
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Weichao;Li Longjiao;Xia Ningbo;Zhou Yanqin;Fang Rui;He Lan;Hu Min;Shen Bang;Zhao Junlong

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几种棒状蛋白(ROP)已被证实是来自北美和欧洲的弓形虫株的关键毒力因子。两个活性激酶ROP17和ROP18以及假激酶ROP5被认为是寄生虫在实验室小鼠中毒力的关键决定因素。鉴于来自不同地理区域的弓形虫菌株的遗传多样性,其他菌株的毒力决定因素,特别是与北美和欧洲菌株亲缘关系较远的菌株,尚不清楚。在这项研究中,我们试图研究三个已知的毒力因子对从中国中心分离的I型毒株(T.gHB1)毒力的贡献。我们通过CRISPR-Cas9系统在该本地分离株中分别删除了ROP17和ROP18,以及与GRA7一起删除。随后的小鼠毒力测试表明,T.gHB1中GRA7、ROP17或ROP18的缺失在小鼠中表现出与缺乏相应蛋白的I型RH株相似的衰减。然而,与RH中已报道的双基因敲除相反,T.gHB1中GRA7+ROP17或GRA7+ROP18的双重缺失与ROP17或ROP18单基因敲除相比并未显示出显著的进一步毒力衰减。这些结果表明,GRA7、ROP18和ROP17可能在弓形虫不同遗传株的毒力测定中发挥不同的作用。
Several rhoptry proteins (ROPs) have been confirmed to be critical virulence factors of Toxoplasma gondii strains from North America and Europe. The two active kinases ROP17 and ROP18, and pseudokinase ROP5 were thought to be the key determinants of parasites' virulence in laboratory mice. Given the genetic diversity of Toxoplasma strains from different geographical regions, the virulence determinants in other strains, particularly the ones that are phylogenetically distant to the North American and European strains, are yet to be elucidated. In this study, we sought to examine the contribution of three known virulence factors to the virulence of a type I strain (T.gHB1) isolated from Central China. We deleted ROP17 and ROP18 individually, as well as in combination with GRA7 by the CRISPR-Cas9 system in this local isolate. Subsequent virulence tests in mice indicated that deletion of GRA7, ROP17, or ROP18 in T.gHB1showed similar attenuation in mice as the type I RH strain lacking the corresponding proteins. However, in contrast to the reported double knockouts in RH, double deletions of GRA7 plus ROP17 or GRA7 plus ROP18 in T.gHB1 did not show significant further virulence attenuation compared to the ROP17 or ROP18 single knockouts. These results indicated that GRA7, ROP18 and ROP17 may play different roles in virulence determination in genetically diverse strains of Toxoplasma.
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期刊: PloS one
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发表时间: 2012-12
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作者:
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