大肠杆菌O157：H7 基因组中大量O岛对细菌致病性影响的系统分析及相关作用机理的研究

Escherichia coli O157:H7 is one of the most important human intestinal pathogens, and is a serious threat to human health. In the genome of E. coli O157:H7, there are 177 O islands which are introduced into the genome mediated by lateral gene transfer events. These O islands play important roles in the evolution and formation of E. coli O157:H7. However, now there is very limited knowledge for the relationship between these O islands and pathogenicity, and the mechanisms by which O islands influence the virulence. Through transcriptome analysis, the applicant has found that 107 of 177 O islands are probably related with the ability of E. coli O157:H7 to adhere to host cells and cause diseases. On the basis of this result, in this project we will systematically analyze those O islands which are possibly related with pathogenicity. It will comprehensively reveal the relationship between the O islands and virulence of E. coli O157:H7 for the first time. The key virulence-related genetic elements in the O islands will be identified and investigated in functional level. The regulation mechanisms for the expression of these virulence-related genetic elements in O islands and the coordination between them and genes in core genome will also be studied, which will provide essential information for understanding the regulation network for the pathogenicity of E. coli O157:H7. The results of this project will be useful for comprehensively understanding the virulence mechanism and evolution routes of E. coli O157:H7, and will provide a basis for the improvement of pathogen control.

大肠杆菌 O157:H7是最重要的人类肠道致病菌之一，是人类健康的重要威胁。大肠杆菌 O157:H7中存在着177个由基因横向转移介导进入基因组的特异性O岛，它们在 O157:H7的进化中发挥了关键作用。但目前，人们对于Ｏ岛影响致病性的方式和机理的认识非常有限。申请人前期通过转录组分析发现，107个O岛可能与细菌粘附细胞能力和致病性相关。本项目以此为基础，结合多种技术手段，对一系列可能与致病性相关的O岛进行系统分析和鉴定，将首次系统揭示大量O岛与O157:H7致病性的关系。将发现和鉴定O岛中与致病性相关的一系列关键遗传元件，并解析其作用机理。在此基础上，研究相关元件的调控机制及其与核心基因组中基因的协同作用机制，完善对于大肠杆菌致病性调控网络的认识和理解。项目成果对于全面理解O157:H7这一重要致病菌的致病机理和进化机制具有重要意义，并可为相关防控工作提供新的思路。

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。大肠杆菌O157:H7 在进化过程中通过基因横向转移介导获得了 177 个特异性 O 岛，它们赋予了O157:H7 定植肠道并引起疾病的能力。但绝大多数Ｏ岛对 O157:H7致病性的影响方式和作用机理还不清晰。本项目中，我们研究确定了14个和大肠杆菌 O157:H7 致病性相关的O岛。发现O-119岛上的z4267，O-134岛上的z4802，O-167岛上的z5684和z5692，O-29岛上的z0639，以及O-93岛上的Esr055对大肠杆菌 O157:H7 致病性起关键作用，并深入解析了这些关键遗传元件影响大肠杆菌 O157:H7 致病性的分子机制。项目成果丰富并完善了人们对于大肠杆菌O157:H7致病性调控网络的认识，对于全面理解该致病菌的致病机理和进化机制具有重要意义。本项目发现和鉴定的与大肠杆菌O157:H7致病性相关的关键遗传元件可以作为疫苗和相关药物的候选靶点，为肠道致病菌的预防和治疗提供新的思路。