Targeting quiescent E. coli for prevention of recurrent urinary tract infections

项目负责人/主要研究者（最后一名、第一名、中间名）：Cho，Bongsup P. 项目摘要 在美国，每年大约有1100万例尿路感染（UTI）报告 超过50%的女性将被诊断出至少一种UTI。27%的患者 患有UTI的患者即使在成功的抗生素治疗后，也会在12个月内复发。 尿路致病性大肠杆菌（UPEC）是初始和复发性UTI的主要原因， 通过进入膀胱上皮细胞的静止状态而在抗生素治疗中存活下来， 一旦抗生素治疗停止，在稍后的时间恢复生长。在本研究计划中，我们将 基础研究，以帮助更好地了解和治疗复发性尿路感染， 影响妇女健康。我们建议合成，鉴定和表征分子， 体外模型系统中的UPEC静止，以告知可能的开发候选药物 治疗复发性尿路感染的药物。到目前为止，我们已经确定了几种分子， 作为诱导静止期UPEC增殖的线索，使细菌细胞能够重新获得抗生素， 灵敏度 罗得岛IDEA生物医学研究网络（RI-INBRE）计划的总体目标 是为了提高机构的研究能力，以实现生物医学的卓越和实践的学生培训， RI.这项工作建议与本补充将进行在一个主要的本科院校 (PUI)在国际扶轮，Salve Regina大学（Susan Meschwitz博士），与罗德岛大学合作 岛上的调查人员（乔迪·坎伯格博士和大卫罗利博士）。RI-INBRE之前对Meschwitz的资助 实验室为15名本科生提供了研究机会，其中许多人已经合作， 撰写同行评议的出版物，并攻读高级学位。这个补充项目福尔斯 在环境健康科学的广泛科学专题领域内， 合成小肽，作为环境线索，以改变尿路疾病的过程 感染.这项研究与RI-INBRE计划的既定目标一致，包括：（1） 提高PUI教师在发展生产力和可持续的实践学生培训计划;（2） 促进PUI和URI教师研究人员之间的强有力合作;以及（3）增加参与 PUI和社区大学的学生在URI的研究活动。 PHS 398（修订版03/2020批准至02/28/2023）OMB编号0925-0001 第5页

Program Director/Principal Investigator (Last, First, Middle): Cho, Bongsup P. PROJECT SUMMARY In the United States, there are approximately 11 million urinary tract infections (UTIs) reported each year and more than 50% of women will be diagnosed with at least one UTI. Twenty-seven percent of patients with a UTI experience a recurrence within 12 months, even after successful antibiotic treatment. Uropathogenic Escherichia coli (UPEC), a leading cause of initial and recurring UTIs, are thought to survive antibiotic treatment by entering a quiescent state in bladder epithelial cells, which allows them to resume growth at a later time once antibiotic treatment is halted. In this research plan, we will conduct basic research to help better understand and treat recurrent urinary tract infections, which significantly impact women’s health. We propose to synthesize, identify and characterize molecules that reverse UPEC quiescence in an in vitro model system to inform on possible lead candidates for the development of therapeutic agents to treat recurrent UTIs. To date, we have identified several molecules that function as cues to induce proliferation of quiescent UPEC, enabling the bacterial cells to regain antibiotic- sensitivity. The overarching goal of the Rhode Island IDeA Network of Biomedical Research (RI-INBRE) program is to improve institutional research capacity for biomedical excellence and hands-on student training in RI. The work proposed with this supplement will be carried out at a primarily undergraduate institution (PUI) in RI, Salve Regina University (Dr. Susan Meschwitz), in collaboration with University of Rhode Island investigators (Dr. Jodi Camberg and Dr. David Rowley). Prior RI-INBRE funding to the Meschwitz laboratory has provided research opportunities for 15 undergraduate students, many of whom have co- authored peer-reviewed publications and pursued advanced degrees. This supplemental project falls within the broad scientific thematic area of Environmental Health Sciences by proposing to develop and synthesize small peptides that function as environmental cues to alter the course of uropathogenic infections. This research is aligned with the stated aims of the parent RI-INBRE program, including: (1) improve PUI faculty in developing productive and sustainable hands-on student training programs; (2) promote strong collaboration between PUI and URI faculty investigators; and (3) increase participation of PUI and community college students in research activities at URI. PHS 398 (Rev. 03/2020 Approved Through 02/28/2023) OMB No. 0925-0001 Page 5