A Yersinia T6SS Effector YezP Engages the Hemin Uptake Receptor HmuR and ZnuABC for Zn2+ Acquisition
A Yersinia T6SS Effector YezP Engages the Hemin Uptake Receptor HmuR and ZnuABC for Zn2+ Acquisition
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DOI：
10.1128/aem.00240-23
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发表时间：
2023-06-20
影响因子：
4.4
通讯作者：
Shen，Xihui
中科院分区：
文献类型：
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作者：
Liu，Hai;Wei，Zhiyan;Shen，Xihui
金属离子是所有生命形式的必需营养素，限制金属离子的可用性是宿主抵御细菌感染的有效方法。与此同时，细菌病原体已经开发出同样有效的手段来确保其金属离子供应。发现肠道病原体假结核耶尔森氏菌使用T6 SS 4效应子YezP摄取锌，这对于Zn 2+获取和氧化应激下的细菌存活是必需的。然而，这种锌吸收途径的机制尚未完全阐明。在这里，我们鉴定了YezP的氯化血红素摄取受体HmuR，其可以通过YezP-Zn 2+复合物介导Zn 2+输入到周质中，并证明YezP在细胞外发挥作用。本研究还证实ZnuCB转运蛋白是Zn 2+从周质到细胞质的内膜转运蛋白。总的来说，我们的结果揭示了完整的T6 SS/YezP/HmuR/ZnuABC途径，其中多个系统耦合以支持Y的锌摄取。重要性在细菌病原体中鉴定在正常生理生长条件下参与金属离子输入的转运蛋白将阐明其致病机制。Y.假结核病YPIII是一种常见的食源性病原体，感染动物和人类，通过T6 SS 4效应子YezP摄取锌。然而，外部和内部的运输参与Zn 2+的收购仍然是未知的。本研究的重要成果是鉴定了氯化血红素摄取受体HmuR和内膜转运蛋白ZnuCB，它们通过YezP-Zn 2+复合物将Zn 2+导入细胞质，并阐明了由T6 SS、HmuRSTUV和ZnuABC组成的完整的Zn 2+获取途径，从而提供了T6 SS介导的离子转运及其功能的全面视图。
Metal ions are essential nutrients for all life forms, and restriction of metal ion availability is an effective host defense against bacterial infection. Meanwhile, bacterial pathogens have developed equally effective means to secure their metal ion supply. The enteric pathogen Yersinia pseudotuberculosis was found to uptake zinc using the T6SS4 effector YezP, which is essential for Zn2+acquisition and bacterial survival under oxidative stress. However, the mechanism of this zinc uptake pathway has not been fully elucidated. Here, we identified the hemin uptake receptor HmuR for YezP, which can mediate import of Zn2+into the periplasm by the YezP-Zn2+complex and demonstrated that YezP functions extracellularly. This study also confirmed that the ZnuCB transporter is the inner membrane transporter for Zn2+from the periplasm to cytoplasm. Overall, our results reveal the complete T6SS/YezP/HmuR/ZnuABC pathway, wherein multiple systems are coupled to support zinc uptake by Y. pseudotuberculosis under oxidative stress.IMPORTANCEIdentifying the transporters involved in import of metal ions under normal physiological growth conditions in bacterial pathogens will clarify its pathogenic mechanism. Y. pseudotuberculosis YPIII, a common foodborne pathogen that infects animals and humans, uptake zinc via the T6SS4 effector YezP. However, the outer and inner transports involved in Zn2+acquisition remain unknown. The important outcomes of this study are the identification of the hemin uptake receptor HmuR and inner membrane transporter ZnuCB that import Zn2+into the cytoplasm via the YezP-Zn2+complex, and elucidation of the complete Zn2+acquisition pathway consisting of T6SS, HmuRSTUV, and ZnuABC, thereby providing a comprehensive view of T6SS-mediated ion transport and its functions.