Li Bingqing, Yue Yingying, Yuan Zenglin, Zhang Fengyu, Li Peng, Song Nannan, Lin Wei, Liu Yan, Yang Yinlong, Li Zhihui, Gu Lichuan
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan 250100, China.
Nucleic Acids Res. 2017 Sep 29;45(17):9976-9989. doi: 10.1093/nar/gkx656.
Salmonella reduces flagella biogenesis to avoid detection within host cells by a largely unknown mechanism. We identified an EAL-like protein STM1697 as required and sufficient for this process. STM1697 surges to a high level after Salmonella enters host cells and restrains the expression of flagellar genes by regulating the function of flagellar switch protein FlhD4C2, the transcription activator of all other flagellar genes. Unlike other anti-FlhD4C2 factors, STM1697 does not prevent FlhD4C2 from binding to target DNA. A 2.0 Å resolution STM1697-FlhD structure reveals that STM1697 binds the same region of FlhD as STM1344, but with weaker affinity. Further experiments show that STM1697 regulates flagella biogenesis by restricting FlhD4C2 from recruiting RNA polymerase and the regulatory effect of STM1697 on flagellar biogenesis and virulence are all achieved by interaction with FlhD. Finally, we describe a novel mechanism mediated by STM1697 in which Salmonella can inhibit the production of flagella antigen and escape from the host immune system.
沙门氏菌通过一种 largely unknown 机制减少鞭毛生物合成以避免在宿主细胞内被检测到。我们鉴定出一种 EAL 样蛋白 STM1697 对此过程是必需且充分的。沙门氏菌进入宿主细胞后，STM1697 激增到高水平，并通过调节鞭毛开关蛋白 FlhD4C2（所有其他鞭毛基因的转录激活因子）的功能来抑制鞭毛基因的表达。与其他抗 FlhD4C2 因子不同，STM1697 不会阻止 FlhD4C2 与靶 DNA 结合。分辨率为 2.0 Å 的 STM1697 - FlhD 结构表明，STM1697 与 STM1344 结合 FlhD 的相同区域，但亲和力较弱。进一步实验表明，STM1697 通过限制 FlhD4C2 招募 RNA 聚合酶来调节鞭毛生物合成，并且 STM1697 对鞭毛生物合成和毒力的调节作用均通过与 FlhD 的相互作用实现。最后，我们描述了一种由 STM1697 介导的新机制，其中沙门氏菌可以抑制鞭毛抗原的产生并逃避宿主免疫系统。
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