细菌表面多糖抗原（O抗原、K抗原等）在宿主免疫系统长期压力下形成了自然界中最丰富的生物多样性之一，是重要的免疫原性物质和致病因子。在青年科学基金项目中，申请人通过对大肠杆菌等细菌O抗原基因簇的系统比较分析和O抗原化学结构的解析，对于细菌表面多糖抗原多样性的形成方式有了较为深入的认识，相关结果已发表19篇SCI论文。目前，对于O抗原合成基因的功能研究尚存在较多空白。罕见单糖和寡糖在多糖抗原多样性的形成中起到重要作用，其有助于细菌逃避宿主细胞的免疫识别，并在生物制药等领域具有应用价值。本项目将鉴定一系列前期研究中新发现的罕见单糖生物合成途径；解析多个参与致病菌表面多糖抗原合成的糖基转移酶的功能，并解析其作用机制。O 抗原的侧链修饰已被报道可影响志贺氏菌的致病性和流行能力，本项目将利用比较基因组学等方法，系统发现和鉴定负责大肠杆菌和沙门氏菌O抗原侧链修饰的相关基因，并解析其侧链修饰机制。

Bacterial surface polysaccharide antigen, such as O-antigen and K-antigen, exhibits one of the richest diversities in nature due to long-term pressure from the host immune system. It contributes major antigenic variability to the cell surface, and plays essential roles in the virulence and host adaptation of bacteria. Under the support by National Natural Science Foundation of Youth Science Fund project, the applicant’s work, including systematical comparative analysis of bacterial O-antigen gene clusters and structural analysis of polysaccharide antigens, has improved our understanding for the formation process of bacterial surface polysaccharide antigen diversity. In that project, a total of 19 SCI papers have been published up to now. Currently, there are still many gaps in the knowledge about the function of genes involved in the synthesis of O-antigen. Unique monosaccharides and oligosaccharides play important roles in the formation of bacterial surface polysaccharide diversity, and are beneficial for bacteria escaping from host immune recognition. Unique monosaccharides and oligosaccharides are also valuable in the filed of biopharmaceuticals. This project will identify several novel biosynthesis pathways for unique monosaccharides. It will also identify the function of several glycosyltransferases involved in the synthesis of surface antigens from important pathogens, and study the functional mechanism of these enzymes. The side chain modification of O-antigen has been reported to be related with the pathogenicity of Shigella. This project will systematically identify the genes responsible for the O-antigen modification of Escherichia coli and Salmonella, through the research methods of comparative genomics, molecular biology and etc, and elucidates their functional mechanism.