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UPEC gains access to the urinary tract through mucosal reservoirs, including the vaginal tract. With rising antibiotic resistance and frequent recurrence, alternative non-antibiotic strategies like bacteriophage (phage) therapy are gaining attention. We explored the potential of a lytic phage, \u03a6HP3, as well as a phage cocktail to decolonize UPEC from the urogenital tract using\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models. Phage demonstrated replication and lytic activity in both bacteriologic medium and simulated vaginal fluid. Pretreatment of human vaginal epithelial cells (VK2\/E6E7) and bladder carcinoma cells (HTB-9) with phage reduced adhesion and invasion of UPEC compared with controls. Phage treatment was further able to reduce intracellular UPEC in VK2 cells. Notably, phage pretreatment did not impact phage-resistant UPEC strains, indicating that phage lysis was the primary driver of phenotypes. Live confocal microscopy confirmed the interaction of phage particles with UPEC and with both epithelial cell lines.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      , daily intravaginal \u03a6HP3 administration in humanized microbiota mice significantly reduced vaginal UPEC burden after 4 days. Treatment with a phage cocktail also reduced vaginal and cervical tissue burdens by day 7 post-treatment. UPEC dissemination was observed in uterine and kidney tissues, but burdens were not different between phage and mock-treated groups. In conclusion, we demonstrate that phage and phage cocktails can modestly reduce UPEC urogenital colonization, highlighting the potential of phage therapy as a viable prevention strategy for UTI.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00543-25","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:44:31Z","timestamp":1772117071000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Bacteriophage-mediated reduction of uropathogenic\n                    <i>E. coli<\/i>\n                    from the urogenital epithelium"],"prefix":"10.1128","volume":"94","author":[{"given":"Bishnu","family":"Joshi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine","place":["Houston, 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