肠道是致病菌感染人类的主要器官。不同的肠道致病菌选择不同的肠道部位定植、侵染，其致病过程中的关键步骤包括： 1）逃避宿主免疫攻击；2）识别定植位点，激活致病基因表达，吸附或侵入肠道上皮细胞；3）引起肠道组织病变。人们对第三个步骤的认识较清晰，但针对前两个步骤的研究相对较少。本项目以具有代表性的肠出血性大肠杆菌（EHEC）为素材，系统研究其“如何精确识别定植位点（大肠），快速吸附定植”和“如何逃避免疫攻击”。一方面，全面揭示肠道信号分子与EHEC致病性的关系，解析相关机理，深入认识其致病性调控网络。另一方面，解析O抗原中具有罕见单糖这一特点是否有利于EHEC逃避肠道中SIgA的攻击；并揭示EHEC通过调控O抗原链长来协调逃避免疫攻击和吸附细胞能力之间平衡的机制。项目成果将使我们从整体水平更清晰地认识EHEC的致病机理，并可为EHEC感染的预防和治疗提供新的靶点。

In human, the bacterial pathogen infections occur primarily in intestine. Different bacterial pathogens recognize different intestinal sites for colonization and infection, and the key steps in the pathogenicity process include: 1) escaping from host immune attack; 2) recognizing the colonization site and adhering to or invading intestinal epithelium through regulating the expression of virulence genes; 3) causing intestinal lesions. Mechanisms for the third step has been widely studied, however, the research on the first two steps are relatively limited. This project will focus on the Enterohemorrhagic Escherichia coli (EHEC) strains, which are representative intestinal bacterial pathogens, and systematically analyzed “How EHEC strains recognize their preferred colonization site (human large intestine) to adhere to and colonize human intestine” and “How EHEC strains escape immune attack and adapt to host intestinal environment”. On the first hand, we will systematically explore all potential intestinal signals related to EHEC pathogenicity and relevant regulation mechanisms, to enrich our understanding on overall EHEC virulence regulatory network. On the other hand, we will investigate whether the presence of rare monosaccharide residues in the O-antigen benefits EHEC to escape from the recognition by SIgA in intestinal mucosa. We will also investigate how EHEC strains coordinate the balance between avoidance of immune attack and increasing adherence capacity by regulating the length of O-antigen. The outcome of this project will largely enhance our understanding of EHEC pathogenicity mechanisms, and provide novel ideas and targets to prevent and control EHEC infection.