Copper stress by nutritional immunity activates the CusS-CusR two-component system that contributes to Vibrio alginolyticus anti-host response but affects virulence-related properties
Copper stress by nutritional immunity activates the CusS-CusR two-component system that contributes to Vibrio alginolyticus anti-host response but affects virulence-related properties
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DOI：
10.1016/j.aquaculture.2020.736012
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发表时间：
2021-02-15
期刊：
影响因子：
4.5
通讯作者：
Huang, Lixing
中科院分区：
文献类型：
--
作者：
He, Rongchao;Zuo, Yanfei;Huang, Lixing
铜是细胞功能不可缺少的物质，但高浓度的铜会破坏生物大分子。最近发现铜积累出现在细菌感染发生的地方。这证明铜抗性是细菌致病力的必要条件。几乎所有的细菌，从孤立的环境细菌到人类致病菌，都具有铜耐受机制。我们发现溶藻弧菌（Vibrio alginolyticus）是一种广泛分布于热带沿海地区的新型微生物，具有抗铜磷酸盐调节子CusS-CusR-CusCFBA。Cu 2+处理后，cusS、cusR、cusCFBA、copB和[EC：3.6.3.4]的表达显著上调。这些基因与铜耐性有关，其中cusS和cusR起着关键作用。当cusS和cusR被沉默时，cusCFBA的表达水平也显著降低。出乎意料的是，在cusS和cusR的沉默菌株中，粘附、溶血、生物膜形成、运动性和毒力显著增加。同时，启动子区分析、EMSA和LacZ报告基因分析表明，CusR参与了cusCFBA和多个毒力基因的调控。综上所述，虽然CusSR可以通过调节cusCFBA参与铜耐受机制来赋予宿主防御抗性，但营养免疫引起的铜胁迫对CusSR的激活将降低溶藻弧菌的致病性。
Copper is indispensable for cellular functions, but high levels of copper will destruct biological macromolecules. Copper accumulation was recently found to appear where the bacterial infection took place. This proved that copper resistance is necessary for bacteria virulence. Almost all bacteria, from isolated environmental bacteria to human pathogenic bacteria, have copper tolerance mechanisms. We found Vibrio alginolyticus, an emerging microbe distributed widely in tropical coastal areas, had the copper resistance phosphate regulon CusS-CusR-CusCFBA. After Cu2+ treatment, the expression of cusS, cusR, cusCFBA, copB and [EC:3.6.3.4] were significantly up-regulated. These genes were related to copper tolerance, among which cusS and cusR played a key role. When cusS and cusR were silenced, the expression levels of cusCFBA were also significantly decreased. Unexpectedly, the adhesion, hemolysis, biofilm formation, motility, and virulence were significantly increased in the silencing strains of cusS and cusR. Meanwhile, promoter region analysis, EMSA, and LacZ reporter gene analysis suggested that CusR played a role in the regulation of cusCFBA and multiple virulence genes. Together, these indicated that although CusSR could confer resistance to the host defense by regulating the cusCFBA to participate in the copper tolerance mechanism, the activation of the CusSR by copper stress from nutritional immunity would reduce the V. alginolyticus pathogenesis.