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

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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