Reciprocal Control of Motility and Adherence in UTI

UTI 中运动性和依从性的相互控制

• 批准号: 7172315
• 负责人: HARRY L. MOBLEY
• 金额: $ 35.58万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172315
• 关键词: Acute Cystitis; Adherence; Agar; Area; Bacteremia; Bacteria; Bacterial Adhesins; Bacterial Infections; Biological Assay; Birth; Bladder; Body Surface; Calculi; Carbohydrates; Catheters; Cells; Characteristics; Colon; Data; Deformity; Development; Disease Outbreaks; Enterobacteriaceae; Epithelial; Equilibrium; Escherichia coli; Fimbria of hippocampus; Flagella; Foreign Bodies; Genetic; Genital system; Genus Cola; Growth; Hand; Hospitals; Human; Individual; Infection; Intestines; Kidney; Kidney Calculi; Life; Mediating; Mirabilis; Modeling; Molecular; Mucous body substance; Mus; Newborn Infant; Obstruction; Organelles; Organism; Patients; Pattern; Phase; Physicians; Pilum; Proteus mirabilis; Pyelonephritis; Reflux; Regulation; Regulatory Pathway; Reporting; Research Personnel; Rest; Role; Sampling; Site; Surface; Swimming; Symptoms; Testing; Time; Toxin; Tube; United States; Urethra; Urinary tract; Urinary tract infection; Urine; Urologic Diseases; Uropathogen; Uropathogenic E. coli; Virulence; Virulent; Visit; Woman; ascending urinary tract infection; cell motility; cost; flagellum motility; in vivo; member; pressure; programs; receptor; renal scarring; respiratory; trait; urolithiasis

DESCRIPTION (provided by applicant): The urinary tract is a complicated epithelial-lined tube with an opening to the body surface, making it susceptible to infection by exogenous organisms. Indeed, urinary tract infection is one of the most common bacterial infections of humans and the most common kidney and urologic disease in the U.S. The most common uropathogen, Escherichia coli, can cause acute cystitis or pyelonephritis in the uncomplicated urinary tract. On the other hand, in patients with complicated urinary tracts, ones in which normal urine flow are blocked by structural abnormality or urethral catheters, species such as Proteus mirabilis predominate. Both E. coli and P. mirabilis are members of the Enterobacteriaceae, are motile, and produce a battery of fimbriae by which they mediate adherence to the uroepithelium. The abilities to swim using flagella and to adhere by certain fimbriae have been demonstrated to be virulence traits for both organisms. However the actions of the two organelles have opposite functions. We reason that there is a time to swim and a time to adhere; we also provide preliminary data that E. coli and P. mirabilis possess defined regulatory pathways by which they transform from the motile to the adherent form and wee versa. As well, other regulatory mechanisms have been uncovered. In this proposal, we will test the central hypothesis that uropathogenic E. coli and P. mirabilis regulate the balance between motility and adherence. We will test this hypothesis by carrying out the following specific aims: 1) Determine the mechanism of reciprocal control of motility and adherence; 2) Determine other mechanisms of flagella and fimbriae expression including coordinated expression, selection, and regulation by growth phase; and 3) Demonstrate in vivo the control of motility and adherence. Genetic constructs, molecular assays, microarrays, and a murine model of ascending urinary tract infection will be used to test the hypothesis. Determination of a defined mechanism has implications far beyond the urinary tract. Clearly the ability to colonize mucosal surfaces in the respiratory, intestinal, and genital tracts also require the orchestrated synthesis of fimbriae for adherence and flagella for motility.

描述（由申请人提供）：尿路是一个复杂的上皮管，并向体面开口，使其容易受到外源性生物感染的影响。实际上，尿路感染是人类最常见的细菌感染之一，在美国，最常见的肾脏和泌尿科疾病是最常见的尿路病原体，可引起急性膀胱炎或简单的尿道肾上腺炎。另一方面，在复杂的尿路患者中，正常尿液流动被结构异常或尿道导管所阻断的患者，例如米拉比利斯（Proteus mirabilis）等物种。大肠杆菌和小疟原虫都是肠杆菌科的成员，是运动的，并且产生了一堆纤维化，它们可以介导对牙骨上皮的依从性。已经证明，使用鞭毛并通过某些纤维膜粘附的能力是两种生物的毒力特征。但是，两个细胞器的作用具有相反的功能。我们认为有时间游泳和遵守时间。我们还提供了大肠杆菌和奇异疟原虫具有定义的调节途径的初步数据，它们从摩托学转变为粘附形式，又有wee versa。同样，还发现了其他监管机制。在此提案中，我们将检验一个中心假设，即尿液发育性大肠杆菌和奇异假单胞菌调节运动和粘附之间的平衡。我们将通过执行以下特定目的来检验这一假设：1）确定运动和依从性的相互控制的机制； 2）确定鞭毛和膜状表达的其他机制，包括按生长阶段进行协调的表达，选择和调节； 3）在体内表现出对运动和依从性的控制。遗传构建体，分子测定，微阵列和临时尿路感染的鼠模型将用于检验该假设。确定定义机制的含义远远超出了尿路。显然，在呼吸道，肠道和生殖道中定居的粘膜表面的能力也需要精心策划的纤维化合成，以依从性，而鞭毛则具有运动性。