大肠杆菌O157:H7是最重要的人类肠道致病菌之一，严重威胁人类健康。感知肠道环境信号、进而调控相关毒性基因的表达从而特异地定殖大肠是该菌致病过程中最关键的一步。部分sRNA已被证明可参与其毒性调节和定殖位点识别，但大部分分子机制都不清晰。本项目拟结合高通量组学技术、分子生物学、生物化学等，对前期发现的7个可能和该致病菌致病位点特异性识别相关的sRNA进行深入研究。一方面，确定受该类sRNA调节的靶基因及调节方式；另一方面，探究sRNA的表达受到何种环境信号影响，相关过程需要哪些高级调节因子参与。最终完整解析sRNA影响O157:H7定殖位点特异识别的分子机制。研究成果将使我们从整体水平对该菌中sRNA与致病性之间的关系有一个更清楚的认识，对于全面理解该菌的致病机理和进化机制具有重要意义。同时，与该菌致病性相关的sRNA可作为疫苗和相关药物的候选靶点，为相关预防和治疗提供新思路。

Escherichia coli O157:H7 is one of the most notorious human enteric pathogens worldwide, which poses a serious threat to human health. Sensing gut environmental signals and further regulating the bacterial virulence genes expression to colonize specifically in the human large intestine is the most important step for E. coli O157:H7. Previous studies suggested that many non-coding small RNA (sRNA) of E. coli O157:H7 may be involved in the regulation of the bacterial site-specific colonization, however, most of the underlying mechanisms of these regulations remain unknown. In this project, seven candidate sRNAs that may be involved in the site-specific colonization in large intestine will be chosen for further study using high-throughput sequencing, molecular biological methods and biochemical methods. We will identify and determine the target genes of these sRNAs. Furthermore, we will investigate which and how environmental signals regulate the expression of these sRNAs. Therefore, the results will completely reveal the relationship between the sRNAs of E. coli O157:H7 and the bacterial site-specific colonization in the large intestine, which is of great significance for understanding the pathogenesis and evolution of E. coli O157:H7. Besides, the sRNAs may also serve as potential targets for some medicines or vaccines, which is a new strategy for the treatment of E. coli O157:H7 infection.