文献类型：期刊文献

英文题名：Critical role for a promoter discriminator in RpoS control of virulence in Edwardsiella piscicida

作者：Yin, Kaiyu[1,2,3];Guan, Yunpeng[1];Ma, Ruiqing[1];Wei, Lifan[1];Liu, Bing[4];Liu, Xiaohong[1];Zhou, Xiangshan[1];Ma, Yue[1,3];Zhang, Yuanxing[1,3];Waldor, Matthew K.[1,5,6];Wang, Qiyao[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Fisheries Sci & Food Prod Proc, Qingdao, Shandong, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai, Peoples R China;[4]Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Dept Bioquim & Biol Mol, Barcelona, Spain;[5]Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA;[6]Harvard Med Sch, Boston, MA 02115 USA

年份：2018

卷号：14

期号：8

外文期刊名：PLOS PATHOGENS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000471296200001)】；

基金：This work is supported by grants from National Natural Science Foundation of China (Nos. 31602200 to XL, 31430090 to YZ), the Ministry of Agriculture of China (CARS-47-G17), the Shanghai Pujiang Program (16PJD018), the Science and Technology Commission of Shandong and Shanghai Municipality (2017CXGC0103 and 17391902000). MKW is supported by Howard Hughes Medical Institute (HHMI) (063101), NIH RO1-AI-042347, and China Recruitment Program of High-end Foreign Experts (WQ20143100260). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

摘要：Edwardsiella piscicida is a leading fish pathogen that causes significant economic loses in the aquaculture industry. The pathogen depends on type III and type VI secretion systems (T3/T6SS) for growth and virulence in fish and the expression of both systems is controlled by the EsrB transcription activator. Here, we performed a Tn-seq-based screen to uncover factors that govern esrB expression. Unexpectedly, we discovered that RpoS antagonizes esrB expression and thereby inhibits production of E. piscicida's T3/T6SS. Using in vitro transcription assays, we showed that RpoS can block RpoD-mediated transcription of esrB. ChIP-seq-and RNA-seq-based profiling, as well as mutational and biochemical analyses revealed that RpoS-repressed promoters contain a -6G in their respective discriminator sequences; moreover, this -6G proved critical for RpoS to inhibit esrB expression. Mutation of the RpoS R99 residue, an amino acid that molecular modeling predicts interacts with -6G in the esrB discriminator, abolished RpoS' capacity for repression. In a turbot model, an rpoS deletion mutant was attenuated early but not late in infection, whereas a mutant expressing RpoS(R99A) exhibited elevated fitness throughout the infection period. Collectively, these findings deepen our understanding of how RpoS can inhibit gene expression and demonstrate the temporal variation in the requirement for this sigma factor during infection.