Reciprocal control of motility and adherence in UTI

UTI 中运动性和依从性的相互控制

基本信息

批准号：
8646842
负责人：
HARRY L. MOBLEY
金额：
$ 37.13万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/8646842
关键词：
Acute Cystitis Adherence Agar Antibiotic Resistance Antibiotics Area Bacteremia Bacteria Bacterial Adhesins Bacterial Infections Birth Bladder Bladder Calculi Body Surface Calculi Carbohydrates Catheters Cells Characteristics Colon Data Deformity Development Disease Outbreaks Enterobacteriaceae Epithelial Equilibrium Escherichia coli Flagella Foreign Bodies Genital system Hospitals Human Individual Infection Intestines Kidney Kidney Calculi Kidney Diseases Life Mediating Mirabilis Mucous body substance Newborn Infant Obstruction Operon Organelles Organism Patients Pattern Physicians Prevalence Proteins Proteus mirabilis 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 acute pyelonephritis antimicrobial antimicrobial drug cell motility combat cost fimbria flagellum motility member pressure public health relevance receptor renal scarring resistant strain respiratory trait urinary urolithiasis

项目摘要

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.

描述（申请人提供）：泌尿道是一个复杂的上皮衬里管道，开口通向体表，使其容易受到外源微生物的感染。事实上，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系统疾病。最常见的尿路病原体是大肠杆菌，可在无并发症的尿路中引起急性膀胱炎或肾盂肾炎。另一方面，在患有复杂尿路的患者中，即正常尿流因结构异常或导尿管而受阻的患者中，奇异变形杆菌等物种占主导地位。大肠杆菌和奇异变形杆菌都是肠杆菌科的成员，具有运动性，并产生一系列菌毛，通过菌毛介导对尿上皮的粘附。使用鞭毛游泳和通过某些菌毛粘附的能力已被证明是这两种生物体的毒力特征。然而，这两种细胞器的作用具有相反的功能。我们认为，有游泳的时候，也有坚持的时候。我们还提供了初步数据，表明大肠杆菌和奇异变形杆菌拥有明确的调控途径，通过这些途径它们可以从运动形式转变为粘附形式，反之亦然。此外，还发现了其他监管机制。在本提案中，我们将测试核心假设，即泌尿道致病性大肠杆菌和奇异变形杆菌严格调节运动性和粘附性之间的平衡。我们将通过实现以下具体目标来检验这一假设： 1) 阐明菌毛操纵子编码的运动性抑制因子：PapX 和 MrpJ 的普遍性、功能、结构和对毒力的贡献； 2）定义介导颤动和运动之间相互调节的蛋白质的调节途径。显然，在呼吸道、肠道和生殖道粘膜表面定殖的能力还需要精心合成用于粘附的菌毛和用于运动的鞭毛。