PATHOGENIC MECHANISMS IN URINARY TRACT INFECTIONS

据估计，全球每年发生1.5亿次尿路感染， 直接医疗保健费用为60亿美元。虽然没有综合评估 与尿路感染相关的发病率、死亡率和总成本 经过计算，这些感染显然代表着重大的公共健康 负担。该计划项目提出的研究将改善我们的 了解流行病学、危险因素、微生物生态学、 尿路感染的分子发病机制及预防。该计划的目标 项目将通过多学科的发展来满足 研究团队将合作开展四项相互关联的工作 项目。项目1将描述氢的保护作用 产生过氧化氢的乳杆菌，正常的主要微生物种类 阴道菌群在预防产后感染大肠埃希菌和尿路感染中的作用 年轻女性。该项目最终将测试一种新的方法来 预防妇女尿路感染，即使用高度附着的氢气 产生过氧化氢的乳酸菌菌株经阴道给药 栓剂。在项目2中，膀胱上皮的作用和调节 细胞鞘糖脂作为泌尿系致病菌的附着部位 将使用原代培养的膀胱上皮细胞进行研究。 细菌粘附素与细菌间特异性相互作用的鉴定 上皮细胞鞘糖脂受体可能促进发育 使用局部应用的比较类比的新的预防手段。 项目3将在两种重要的尿路病原体中识别新的毒力基因， 大肠埃希菌和铜绿假单胞菌基因表达研究 实际感染的条件。在项目4中，上皮细胞 DR后被激活的反应和细胞内信号通路 含大肠杆菌菌毛通过加速腐烂附着于上皮细胞 将对影响因素进行研究。实验室核心将提供主要的膀胱 上皮细胞，核糖体分型，尿毒力基因的特征和 其他资源投向项目。行政/生物统计学核心 将协调该项目并提供生物统计学专业知识 项目调查员。拟议的研究将产生新的方法 以预防尿路感染。

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.