Role of E. coli Virulence Factors in Chronic Prostate Infection and Inflammation

大肠杆菌毒力因子在慢性前列腺感染和炎症中的作用

• 批准号: 7315205
• 负责人: WALTER J HOPKINS
• 金额: $ 18.38万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7315205
• 关键词: Acute; Acute Prostatitis; Adult; Affect; Area; Attenuated; Bacteria; Bacterial Adhesins; Bacterial Prostatitis; Cell surface; Cells; Chlamydia; Chronic; Chronic Prostatitis; Clinical; Development; Enterococcus; Epithelial; Escherichia coli; Etiology; Foundations; Genes; Goals; Histologic; Human; Immune response; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Intervention; Klebsiella; Lead; Lesion; Localized; Malignant neoplasm of prostate; Methods; Modeling; Morbidity - disease rate; Mus; Mycoplasma; Neoplasms; Pathogenesis; Pathology; Patients; Play; Property; Prostate; Prostatic; Prostatic Infection; Prostatic Neoplasms; Proteus; Pseudomonas; Reporting; Role; Symptoms; Time; Tissues; Toxin; Trichomonas; Ureaplasma; Urinary tract; Uropathogenic E. coli; Virulence; Virulence Factors; Week; base; day; experience; men; mouse model; mutant; novel; pathogen; prevent; prostatitis

DESCRIPTION (provided by applicant): Estimates are that the various forms of prostatitis affect 9-11% of adult men at any one time, and up to 16% of men have reported having prostatitis symptoms. Bacteria are the primary etiological agents in acute prostatitis and in a some chronic prostatitis cases. The most common isolates in acute infections are uropathogenic E. coli strains. Chronic prostatitis may caused by E. coli, and bacteria such as Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The consequences of chronic prostate infections are not only patient morbidity but the potential for development of preneoplastic lesions due to long-term inflammatory responses generated within prostate tissue. Developing a clearer picture of the virulence properties of pathogens responsible for chronic bacterial prostatitis and host responses to infection are critical to understanding the pathology of prostatitis and etiology of preneoplastic lesions. We have developed a mouse model of acute and chronic prostatitis induced by intraurethral inoculation with uropathogenic E. coli. Histologic features of chronically infected prostates are infiltration of inflammatory cells areas of prostatic epithelial neoplasia (PIN), believed to be a precursor to prostate cancer. We believe that PIN lesions in mice may have resulted from inflammation-induced cellular oxidative damage. Using this mouse model and our extensive experience in the field of E. coli virulence we propose to define relationships between specific E. coli virulence factors, acute and chronic infections, and the pathology induced by long-term infection and inflammation. The objectives of this proposal are to 1) define E. coli virulence factors associated with acute prostate infection, 2) utilize these results to define which of those virulence factors are important for chronic prostate infections, and 3) elucidate the relationships between virulence properties of E. coli, chronic inflammatory responses, and development of preneoplastic lesions. Results from these studies will not only identify those E. coli virulence factors contributing to prostate infection but also those that may play a direct or indirect role in inducing PIN. This information can be used to develop novel treatment interventions for infection and PIN development. Chronic prostatitis in an important clinical problem not only because of patient morbidity but also recent evidence that long-term prostatic inflammation may play a role in development of prostate cancer. The primary objective of the proposed studies is to define E. coli genes associated with acute and chronic prostate infection. Secondarily, we will investigate which E. coli genes play a direct or indirect role in development of prostatic lesions. Results of these studies can lead to new methods to prevent or treat chronic bacterial prostatitis.

描述（由申请人提供）：估计是，各种形式的前列腺炎一次都会影响9-11％的成年男性，并且多达16％的男性报告患有前列腺炎症状。细菌是急性前列腺炎和一些慢性前列腺炎病例的主要病因。急性感染中最常见的分离株是肝癌大肠杆菌菌株。大肠杆菌可能引起的慢性前列腺炎，以及诸如克雷伯氏菌，proteus，pseudomonas和肠球菌种类的细菌。慢性前列腺感染的后果不仅是患者的发病率，而且由于前列腺组织中产生的长期炎症反应而导致的肿瘤性病变的发展潜力。对导致慢性细菌前列腺炎和宿主对感染的病原体的毒力特性的更清晰图像对于理解前列腺炎的病理和肿瘤性病变病因的病理至关重要。我们已经开发了一种由尿道发病大肠杆菌接种吞噬的急性和慢性前列腺炎的小鼠模型。长期感染前列腺的组织学特征是前列腺上皮肿瘤（PIN）的炎性细胞区域的浸润，被认为是前列腺癌的先驱。我们认为，小鼠的销损伤可能是由于炎症诱导的细胞氧化损伤而引起的。使用这种小鼠模型以及我们在大肠杆菌毒力领域的丰富经验，我们建议定义特定的大肠杆菌毒力因子，急性和慢性感染以及长期感染和炎症引起的病理之间的关系。该提案的目的是1）定义与急性前列腺感染相关的大肠杆菌毒力因子，2）利用这些结果来定义哪些毒力因子对慢性前列腺感染至关重要，而3）阐明了大肠杆菌的毒力之间的关系，慢性炎症反应，慢性炎性反应和促进性易生化性易生化性的发展。这些研究的结果不仅将确定导致前列腺感染的那些大肠杆菌毒力因子，而且还可以确定那些可能在诱导PIN中发挥直接或间接作用的大肠杆菌毒力因子。这些信息可用于开发新的治疗干预措施，以进行感染和引脚发育。重要的临床问题中的慢性前列腺炎不仅是因为患者发病率，而且还证明长期前列腺炎症可能在前列腺癌的发展中起作用。拟议研究的主要目标是定义与急性和慢性前列腺感染相关的大肠杆菌基因。其次，我们将研究哪些大肠杆菌基因在前列腺病变的发展中起着直接或间接的作用。这些研究的结果可能导致预防或治疗慢性细菌前列腺炎的新方法。