NSRRC Supplement for Duke CTSA Collaboration

杜克大学 CTSA 合作的 NSRRC 补充资料

• 批准号: 7744097
• 负责人: LELA K. RILEY
• 金额: $ 52.89万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744097
• 关键词: NSRRC; Supplement; Duke; CTSA; Collaboration

DESCRIPTION (provided by applicant): The goal of this project is for the NSRRC and the MMRRC at the University of Missouri (MU) to work with the Duke University (Duke) CTSA to utilize existing mouse and pig animal models for discovery of drugs to treat Urinary tract infection (UTI). Urinary tract infections (UTIs) are the second most common type of infection in humans, costing $1.6 billion per year (US) and $90 million in antibiotics alone. Rising antibiotic resistance and the emergence of difficult-to-treat bacteria have complicated contemporary therapy, particularly limiting oral treatment options. We have discovered that uropathogenic Escherichia coli (UPEC), the leading cause of UTIs, invades into the bladder epithelium in cAMP-regulated fusiform vesicles to cause bladder infections (cystitis). Treatment of experimental cystitis with cAMP-elevating drugs results in expulsion of internalized bacteria and attenuation of infection. We hypothesize that cAMP modulation therapy will be widely effective against UPEC and non-UPEC uropathogens, including muti-drug resistant organisms. cAMP modulation therapy may also be employed as an antibioticsparing therapy in UTI associated with neurogenic bladder. We will use comparative experimental models of cystitis in mice and pigs to identify highly efficacious cAMP modulators in the treatment of cystitis. Experimental UTI will also be studied in 5-hydroxytryptamine 3a knockin mice that have a neurogenic bladder phenotype, demonstrating an antibiotic-sparing therapy for this recurrent UTI-associated disease. Together, these studies will demonstrate the cross-mammalian species effects of cAMP modulation therapy on UTI, elucidate its novel role as therapy for difficult to treat infections, and yield specific agents for future human clinical trials. PUBLIC HEALTH RELEVANCE (provided by applicant): Urinary tract infection is the second most common type of infection In humans and accounts for $1.6 billion in US annual health care costs with almost $90 million in prescription antibiotics alone. The goal of this project is for the National Swine Resource and Research Center (NSRRC) and the Mutant Mouse Regional Resource Center (MMRRC) at the University of Missouri to work with the Duke University CTSA to utilize existing mouse and pja animal models for discoverv of drugs to treat Urinary tract infection.

描述（由申请人提供）：该项目的目的是供NSRRC和密苏里大学（MU）的MMRRC与Duke University（DUKE）CTSA合作，以利用现有的小鼠和猪动物模型来发现药物来治疗泌尿道感染（UTI）。尿路感染（UTI）是人类第二常见的感染类型，每年耗资16亿美元（美国）和9000万美元的抗生素。抗生素耐药性的上升和难以治疗的细菌的出现具有复杂的当代治疗，尤其是限制口服治疗方案。我们发现，尿道疾病大肠杆菌（UPEC）是UTI的主要原因，它在cAMP调节的梭形囊泡中侵入膀胱上皮引起膀胱感染（膀胱炎）。用cAMP升高药物治疗实验性膀胱炎会导致内部细菌的驱逐和感染的衰减。我们假设CAMP调节疗法将对UPEC和非UPEC尿道病（包括抗Muti-Drug抗性生物）有效。 CAMP调节疗法也可以用作与神经源性膀胱相关的UTI的抗生素疗法。我们将使用小鼠和猪的膀胱炎的比较实验模型来鉴定高效的cAMP调节剂治疗膀胱炎。还将在具有神经源性膀胱表型的5-羟色胺3A敲蛋白小鼠中进行实验性UTI研究，这证明了这种复发性UTI相关疾病的抗生素疗法。总之，这些研究将证明CAMP调节疗法对UTI的跨哺乳动物物种的影响，阐明其作为难以治疗感染的疗法的新作用，并产生特定的人类临床试验的特定药物。 公共卫生相关性（由申请人提供）：尿路感染是人类第二常见的感染类型，占美国每年医疗保健费用的16亿美元，仅处方抗生素近9000万美元。该项目的目的是使国家猪资源和研究中心（NSRRC）和密苏里大学的突变小鼠区域资源中心（MMRRC）与杜克大学CTSA合作利用现有的小鼠和PJA动物模型，以发现药物的发现来治疗尿道感染。