PATHOGENIC MECHANISMS IN URINARY TRACT INFECTIONS

据估计，全球每年发生1.5亿例尿路感染， 直接的医疗费用是60亿美元。虽然没有汇总摊款， 与UTI相关的发病率、死亡率和总费用的 据计算，这些感染显然代表了一个重大的公共卫生问题， 负担该计划项目提出的研究，将提高我们的 了解流行病学、风险因素、微生物生态学， UTI的分子发病机制和预防。的目标 该项目将通过发展一个多学科的 研究团队将合作开展四个相互关联的 项目项目1将描述氢的保护作用 过氧化氢产生乳酸杆菌，主要微生物物种的正常 阴道植物群，预防E.大肠埃希菌和UTI 年轻女性。该项目最终将测试一种新的方法， 预防女性UTI，即使用高度粘附的氢 过氧化氢产生菌作为阴道给药 栓剂。在项目2中，膀胱上皮细胞的作用和调节 作为尿路致病菌附着位点的细胞鞘糖脂 将使用膀胱上皮细胞的原代培养物进行研究。 细菌粘附素与细菌粘附素之间特异性相互作用的鉴定 上皮细胞鞘糖脂受体可能促进 使用局部应用的比较类似物的新的预防手段。 项目3将在两种重要的尿路病原体中鉴定新的毒力基因， E.大肠杆菌和铜绿假单胞菌的基因表达研究下， 实际感染的情况。在项目4中，上皮细胞 在Dr. 菌毛E.大肠杆菌通过加速衰变附着在上皮细胞上 将研究因素。实验室核心将提供主要膀胱 上皮细胞，核糖体分型，尿毒力基因的表征， 其他项目资源。行政/生物统计核心 将协调该项目，并提供生物统计专业知识， 项目调查员。拟议的研究将产生新的方法 预防UTI。

An estimated 150 million UTIs occur annually on a global basis, accounting for direct health care costs of $6 billion. While no aggregate assessment of the morbidity, mortality and total costs related to UTIs can be calculated, these infections clearly represent a significant public health burden. This program project proposes studies that will improve our understanding of the epidemiology , risk factors, microbial ecology, molecular pathogenesis and prevention of UTIs. The objectives of the project will be met through the development of a multi-disciplinary research team that will collaborate to carry out four interrelated projects. Project 1 will delineate the protective role of hydrogen peroxide producing lactobacilli, the major microbial species of the normal vaginal flora, in preventing vaginal colonization with E. coli and UTI in young women. The project will ultimately test a novel approach to the prevention of UTI in women, namely, use of a highly adherent hydrogen peroxide producing lactobacillus strain administered as a vaginal suppository. In Project 2, the role and regulation of bladder epithelial cell glycosphingolipids as attachment sites for uropathogenic bacteria will be studied using primary cultures of bladder epithelial cells. Identification of specific interactions between bacterial adhesins and epithelial cell glycosphingolipid receptors may facilitate the development of novel means of prevention using topically applied comparative analogs. Project 3 will identify new virulence genes in two important uropathogens, E. coli and Pseudomonas aeruginosa by studying gene expression under conditions of actual infection. In Project 4, the epithelial cell responses and intracellular signaling pathways that are activated after Dr fimbria bearing E. coli attach to epithelial cells via Decay Accelerating Factor will be studied. A laboratory core will provide primary bladder epithelial cells, ribotyping, characterization of urovirulence genes and other resources to the projects. An Administrative/Biostatistical Core will coordinate the project and provide biostatistical expertise to project investigators. The proposed studies will result in new approaches to the prevention of UTIs.