UREASE--MOLECULAR STUDIES AND ROLE IN PATHOGENESIS

描述（改编自申请人的摘要）：尿素酶起作用。 在尿路细菌感染和 胃十二指肠区域。在感染的两个部位， 通过提供更合适的 成长的环境。脲酶的产生也会增加损害 通过氨对细胞的直接伤害转移到受感染的器官。在 此外，尿路感染的尿素产生细菌， 导致膀胱和肾结石的形成。 产脲酶微生物引起的尿路感染导致 严重的炎症反应该建议检查了尿素酶- 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策略方面发挥重要作用， 限制与这些感染相关的粘膜损伤。 两种最常见的产尿素酶的尿路病原体，斯氏普罗威登斯菌 和奇异变形杆菌，在生长过程中表达尿素酶以响应尿素 介质尿素依赖性表达需要调节蛋白UreR， 其是转录激活因子AraC家族的成员。在 这些研究，尿素-尿素相互作用和机制， 将检查UreR的转录。尿素，在高 在人体尿液中的浓度，能够自由扩散到细菌中， UreR-尿素相互作用是侵染的起始信号 它是在泌尿系统中的代理。因为在泌尿道病原体中 UreR既是环境的传感器，又是环境的激活剂。 转录，研究尿素受体-尿素相互作用是重要的， 确定这种蛋白在感染中的作用。

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.