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: 7781030
• 负责人: HARRY L. MOBLEY
• 金额: $ 37.43万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7781030
• 关键词: Acute Cystitis; Adherence; Agar; Antibiotic Resistance; Antibiotics; Area; Bacteremia; Bacteria; Bacterial Adhesins; Bacterial Infections; Birth; Bladder; Body Surface; Calculi; Carbohydrates; Catheters; Cells; Characteristics; Colon; Data; Deformity; Development; Disease Outbreaks; Enterobacteriaceae; Epithelial; Equilibrium; Escherichia coli; Flagella; Foreign Bodies; Genital system; Hand; Hospitals; Human; Individual; Infection; Intestines; Kidney; Kidney Calculi; Life; Mediating; Mirabilis; Mucous body substance; Newborn Infant; Obstruction; Operon; Organelles; Organism; Patients; Pattern; Physicians; Prevalence; Proteins; Proteus mirabilis; Pyelonephritis; Reflux; Regimen; Regulation; Regulatory Pathway; Reporting; Rest; Sampling; Site; Structure; Surface; Swimming; Symptoms; Testing; Time; Toxin; Tube; United States; Urethra; Urinary tract; Urinary tract infection; Urination; Urine; Urologic Diseases; Uropathogen; Uropathogenic E. coli; Vaccines; Virulence; Virulent; Visit; Woman; antimicrobial; antimicrobial drug; cell motility; combat; cost; fimbria; flagellum motility; member; pressure; public health relevance; receptor; renal scarring; resistant strain; respiratory; trait; urinary; 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 US. 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 vice 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 strictly regulate the balance between motility and adherence. We will test this hypothesis by carrying out the following specific aims: 1) Elucidate the prevalence, function, structure, and contribution to virulence of fimbrial operon-encoded repressors of motility: PapX and MrpJ; and 2) Define the regulatory pathways for proteins that mediate reciprocal regulation between fimbriation and motility. 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. PUBLIC HEALTH RELEVANCE: The urinary tract is susceptible to infection by bacteria. Indeed, urinary tract infection is one of the most common bacterial infections of humans. The most common bacterium that infects the urinary tract of healthy individuals is Escherichia coli. On the other hand, in patients who have urinary catheters to help with urination, a bacterium called Proteus mirabilis often infects the bladder and causes stones to form there. Both of these bacteria can either stick to the surface of the bladder or swim up to the kidneys. But they should not do both. This study will determine how these bacteria decide to stick or decide to swim. Understanding how these bacteria cause urinary tract infection will help us to develop antimicrobial agents and vaccines to combat these infections that each year costs the United States nearly 3 billion dollars to treat.

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，也是美国最常见的肾脏和泌尿科疾病。最常见的尿路病大肠杆菌会在简单的尿路中引起急性膀胱炎或肾盂肾炎。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假单胞菌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，反之亦然。同样，还发现了其他监管机制。在此提案中，我们将检验以下中心假设，即尿液发育性大肠杆菌和奇异疟原虫严格调节运动和依从性之间的平衡。我们将通过执行以下特定目的来检验这一假设：1）阐明运动性纤维操纵子编码的毒力的毒力的患病率，功能，结构和贡献：papx和mrpj; 2）定义介导膜片和运动之间相互调节的蛋白质的调节途径。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。 公共卫生相关性：尿路容易受到细菌感染的影响。实际上，尿路感染是人类最常见的细菌感染之一。感染健康个体尿路的最常见细菌是大肠杆菌。另一方面，在有尿导管以帮助排尿的患者中，一种称为mirabilis的细菌通常会感染膀胱并导致石头在那里形成。这两种细菌既可以粘在膀胱的表面，也可以游到肾脏上。但是他们不应该同时做。这项研究将确定这些细菌如何决定坚持或决定游泳。了解这些细菌如何引起尿路感染将有助于我们开发抗菌剂和疫苗，以应对每年花费美国近30亿美元来治疗的这些感染。