Type VI Secretion System Transports Zn2+ to Combat Multiple Stresses and Host Immunity.

Type VI Secretion System Transports Zn2+ to Combat Multiple Stresses and Host Immunity.
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VI 型分泌系统运输 Zn2 以对抗多重应激和宿主免疫力

DOI:
10.1371/journal.ppat.1005020
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发表时间:
2015-07
期刊:
影响因子:
6.7
通讯作者:
Shen X
Shen X
中科院分区:
医学1区
文献类型:
--
作者:
Wang T;Si M;Song Y;Zhu W;Gao F;Wang Y;Zhang L;Zhang W;Wei G;Luo ZQ;Shen X

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VI型分泌系统(T6 SSs)是广泛存在的多组分机器,其将效应子易位到真核或原核细胞中,用于毒力或用于细菌间竞争。在此,我们报告,T6 SS-4从假结核耶尔森氏菌显示出一个意想不到的功能,在运输Zn 2+,以打击不同的压力和宿主免疫。氧化应激等环境损伤通过OxyR诱导T6 SS-4的表达,OxyR是一种转录因子,也调节许多氧化反应基因。锌转运是通过T6 SS-4介导的一种新的Zn 2+结合蛋白底物YezP(YPK_3549)的易位来实现的,该底物在加入细胞外环境时具有拯救T6 SS-4突变体所表现出的对氧化应激的敏感性的能力。经典锌转运蛋白ZnuABC与T6 SS-4或yezP一起的破坏导致几乎完全失去对小鼠的毒力的突变体,进一步突出了T6 SS-4在抵抗宿主免疫中的重要性。这些结果为T6 SS赋予了一种非常规的作用,这将为研究细菌摄取金属离子的新机制以及这一过程在抵抗宿主免疫和在有害环境中生存中的作用奠定基础。
Type VI secretion systems (T6SSs) are widespread multi-component machineries that translocate effectors into either eukaryotic or prokaryotic cells, for virulence or for interbacterial competition. Herein, we report that the T6SS-4 from Yersinia pseudotuberculosis displays an unexpected function in the transportation of Zn2+ to combat diverse stresses and host immunity. Environmental insults such as oxidative stress induce the expression of T6SS-4 via OxyR, the transcriptional factor that also regulates many oxidative response genes. Zinc transportation is achieved by T6SS-4-mediated translocation of a novel Zn2+-binding protein substrate YezP (YPK_3549), which has the capacity to rescue the sensitivity to oxidative stress exhibited by T6SS-4 mutants when added to extracellular milieu. Disruption of the classic zinc transporter ZnuABC together with T6SS-4 or yezP results in mutants that almost completely lost virulence against mice, further highlighting the importance of T6SS-4 in resistance to host immunity. These results assigned an unconventional role to T6SSs, which will lay the foundation for studying novel mechanisms of metal ion uptake by bacteria and the role of this process in their resistance to host immunity and survival in harmful environments.
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