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UREASE--MOLECULAR STUDIES AND ROLE IN PATHOGENESIS

脲酶--分子研究及其在发病机制中的作用

基本信息

批准号：
2802871
负责人：
CARLEEN M. COLLINS
金额：
$ 2.68万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-05-12 至 2000-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (Adapted from Applicant's Abstract): Urease plays a significant role in bacterial infections of both the urinary tract and the gastroduodenal region. At both sites of infection urease enhances the survival of the infecting organism by providing a more suitable environment for growth. The production of urease also increases damage to the infected organs by direct cellular injury from ammonia. In addition, urinary tract infections with a urea-producing bacteria can result in the formation of bladder and kidney stones. Infection of the urinary tract by urease-producing organisms results in a severe inflammatory response. This proposal examines the urease- specific inflammatory response, since it may lead to renal dysfunction and ultimately glandular scarring or destruction. Our results will be compared to the significant inflammation associated with infection by the urease- producing gastroduodenal pathogen Helicobacter pylori. Understanding the mechanisms of the host response to urease-positive organisms will be important in the development of novel strategies to limit mucosal damage associated with these infections. The two most common urease-producing uropathogens, Providencia stuartii and Proteus mirabilis, express urease in response to urea in the growth medium. Urea-dependent expression requires the regulatory protein UreR, which is a member of the AraC-family of transcriptional activators. In these studies, the UreR-urea interaction and the mechanisms of transcription by UreR will be examined. Urea, which is in high concentrations on human urine, is able to freely diffuse into bacteria, and the UreR-urea interaction is an initial signal to the infecting agent that it is in the urinary tract. Since in urinary tract pathogens UreR is acting as both a sensor of the environment and an activator of transcription, studies on the UreR-urea interaction are important for defining the role of this protein in infection.

描述(改编自申请者摘要)：尿素酶起到了在尿路和尿路细菌感染中的重要作用胃十二指肠区域。在感染的两个部位，尿素酶增强通过提供一种更合适的为成长创造环境。尿素酶的产生也会增加损害。氨气对受感染的器官造成直接的细胞损伤。在……里面此外，尿路感染中的一种产尿素细菌可能导致膀胱和肾结石的形成。尿素酶产生菌的尿路感染导致严重的炎症反应。这份提案研究了尿素酶- 特异性炎症反应，因为它可能导致肾功能障碍最终导致腺体结疤或破坏。我们的结果将是与感染相关的显著炎症相比，产生尿素酶的胃十二指肠病原体幽门螺杆菌。了解宿主对尿素酶阳性反应的机制生物体将在开发新的战略方面发挥重要作用限制与这些感染相关的粘膜损害。两种最常见的尿素酶产生菌--普罗维登西亚和奇异变形杆菌，在生长过程中表达尿素酶以响应尿素 5~6成熟。尿素依赖的表达需要调节蛋白URIR，它是转录激活剂家族AraC的成员。在……里面本研究对尿素与尿素的相互作用及其作用机理进行了研究。将检查URR的抄写。尿素，这是在高在人类尿液中的浓度，能够自由扩散到细菌中，尿素-尿素相互作用是感染的初始信号。它是在尿路里的。因为在尿路中的病原体 URER既是环境的传感器，也是环境的激活剂转录，尿素-尿素相互作用的研究对确定了这种蛋白质在感染中的作用。