The Central Metabolism Regulator EIIAGlc Switches Salmonella from Growth Arrest to Acute Virulence through Activation of Virulence Factor Secretion
The Central Metabolism Regulator EIIAGlc Switches Salmonella from Growth Arrest to Acute Virulence through Activation of Virulence Factor Secretion
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DOI：
10.1016/j.celrep.2014.04.022
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发表时间：
2014-06-12
期刊：
影响因子：
8.8
通讯作者：
Bumann, Dirk
中科院分区：
文献类型：
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作者：
Maze, Alain;Glatter, Timo;Bumann, Dirk
沙门氏菌致病的能力取决于代谢活动和毒力因素。在这里，我们展示了一种关键的代谢蛋白EIIA(GLC)，在小鼠伤寒模型中，它对急性感染是绝对必要的，但对沙门氏菌的生存不是必需的。令人惊讶的是，依赖于磷酸化的EIIA GLC功能，包括碳水化合物转运和激活腺苷环化酶以进行全球调节，并不能解释这种毒力表型。相反，生化研究、体外分泌和易位分析以及体内遗传上位性实验表明，EIIA Glc与参与系统毒力的3型分泌系统2(TTSS-2)结合，稳定其细胞质部分，包括关键的TTSS-2 ATPase，并激活毒力因子的分泌。EIIA GLC的这种意想不到的作用揭示了沙门氏菌中心代谢和关键毒力机制之间的显著直接联系。
The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIA(Glc), is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIA Glc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIA Glc binds to the type three secretion system 2 (TTSS-2) involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIA Glc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism.