超过75%的医院尿路感染与导尿管有关，高达16%的患者住院期间使用导尿管，每年用于导管相关性尿路感染的花费超过30亿。针对传统抗菌型导尿管有效时间短、抗菌剂量有限、生物相容性差、易产生耐药性、缺乏治疗功能等缺点，本项目提出利用甘露糖分子修饰导尿管表面促进益生菌生物膜形成的策略，持续抵抗致病菌定植并治愈感染。我们拟从益生菌粘附素FimH蛋白质与甘露糖配体特异性作用出发，设计合成不同糖苷配基取代的甘露糖衍生物，通过空间位阻、非共价作用以及共价键增强FimH蛋白质与甘露糖衍生物的结合力，优化甘露糖配体结构。藉此，通过进一步调控优化配体在导尿管表面的分布和密度，研究影响生物膜形成的因素，构筑高覆盖率、稳定的生物膜保护层。在此基础上，构建导尿管模型装置，考察该策略的可行性和实用性，并对导尿管内细菌干扰、致病菌定植过程进行研究。本研究将对细菌表面粘附行为获得全新的认识，为其他医疗器械污染防治提供参考。

More than 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 16% of hospitalized patients. The costs of catheter-associated urinary tract infections (CAUTI) are in excess of 3 billion RMB/year. The current antimicrobial coatings for urinary catheter have problems with antimicrobial efficacy that deteriorates rather quickly, limited dose, poor biocompatiblity, multidrug resistance and recurrent infections. The proposed research is to develop a new strategy by utilizing mannoside modification of the urinary catheter surface as a means to encourage formation of a protective benign biofilm that prevent catheter colonization by pathogens and associated bacterial infection. We propose to focus on the benign E. coli adhesin FimH-mannose specific binding. Mannosides with varied glycosidic linkages are designed and synthesized, through steric hindrance, non-covalent interaction and covalent bonding, to enhance the binding affinity towards FimH and optimize the mannoside ligands. Afterwards, we will experiment with patterning and density of ligand presentation on the urinary catheter and study the factors that drive biofilm formation on surfaces, in order to create a robust and durable biofilm with optimal protective capability. On this basis, we will construct a catheter model to study feasibility and practicality of this strategy, and investigate the process of bacterial interference and pathogen colonization during catheterization. In the project, we will gain knowledge about the interaction of bacteria with surfaces that will be relevant to the entire field of biofilm infections of biomedical devices.