沈锡辉等《Nature Communications》2022年

论文题目:A secreted effector with a dual role as a toxin and as a transcriptional factor

论文作者：Dandan Wang#, Lingfang Zhu#, Xiangkai Zhen#, Daoyan Yang, Changfu Li, Yating Chen, Huannan Wang, Yichen Qu, Xiaozhen Liu, Yanling Yin, HuaweiGu, Lei Xu, Chuanxing Wan, Yao Wang, Songying Ouyang* and Xihui Shen*

论文摘要：Bacteria have evolved multiple secretion systems for delivering effector proteins into the cytosol of neighboring cells, but the roles of many of these effectors remain unknown. Here, we show that Yersinia pseudotuberculosis secretes an effector, CccR, that can act both as a toxin and as a transcriptional factor. The effector is secreted by a type Ⅵsecretion system (T6SS) and can enter nearby cells of the same species and other species (such as E. coli) via cell-cell contact and in a contact-independent manner. CccR contains an N-terminal FIC domain and a C-terminal DNA-binding domain. In Y. pseudotuberculosis cells, CccR inhibits its own expression by binding through its DNA-binding domain to the cccR promoter, and affects the expression of other genes through unclear mechanisms. In E. coli cells, the FIC domain of CccR AMPylates the cell division protein FtsZ, inducing cell filamentation and growth arrest. Thus, our results indicate that CccR has a dual role, modulating gene expression in neighboring cells of the same species, and inhibiting the growth of competitors.

细菌已经进化出多种分泌系统，用于将效应蛋白传递到邻近细胞的细胞质中，但其中许多效应蛋白的作用仍然未知。我们研究发现假结核耶尔森菌分泌一种效应蛋白CccR，它发挥毒素和转录因子的双功能。证实细菌Ⅵ型分泌系统(T6SS)分泌CccR，可通过接触依赖和非接触依赖型两种方式进入自身亲缘细胞和靶标细胞(如大肠杆菌)。CccR除了含有FIC结构域外，还包含一个DNA结合（helix-turn-helix, HTH）结构域。CccR则进入进入亲缘细菌细胞，通过其DNA结合结构域与CccR启动子结合抑制自身毒素基因的表达。CccR进入竞争细菌细胞后，通过AMPylation化修饰细胞分裂关键蛋白FtsZ而抑制“Z”环的形成，从而导致细菌细胞丝状化和生长停滞。因此，我们结果证实细菌T6SS分泌的一个FIC型双功能效应蛋白CccR，其不仅在细菌竞争中发挥功能，还在细菌细胞通讯方面发挥独特的功能。

文章链接：https://www.nature.com/articles/s41467-022-35522-9