2026-10-11T02:59:48Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33997963 2026-09-25T17:25:44Z category_7 category_8 category_12 category_13 category_272 category_46 category_734 category_64 category_132 portal_5 item_type_3 month_year_09_2026

<p>MICs.</p> Kathrin Tomasek (25111129) Kristina Skurvydaite (25111132) Gauri Paduthol (25111135) Allison M. Burns (25111138) Léa Schlunke (21232340) Valentin Borgeat (25111141) Christian Pasquali (503452) Mario Romani (25111144) John D. McKinney (1493986) Medicine Microbiology Cell Biology Genetics Environmental Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer Infectious Diseases targeted lysosomal activation reduces recurrence rates major clinical burden influence treatment outcomes human epithelial models escherichia coli </ epithelial infection models differentiated epithelial monolayers bacteria withstand antibiotics multiple antibiotic classes antibiotic bacterial regrowth uropathogenic escherichia coli globally used therapy bladder epithelial cells antibiotic therapy intracellular uropathogenic bladder organoids bladder epithelium vaxom ), several decades pharmacologically reinforced limits post host defenses clinically approved cellular mechanisms <div><p>Recurrent urinary tract infections (UTIs) are a major clinical burden, driven in part by the ability of uropathogenic Escherichia coli (UPEC) to establish intracellular niches within the bladder epithelium, where bacteria withstand antibiotics and host defenses. The oral bacterial lysate OM-89 (Uro-Vaxom), a clinically approved and globally used therapy for the prevention and management of recurrent UTIs for several decades, reduces recurrence rates, but its cellular mechanisms of action remain incompletely understood. Here, we demonstrate that OM-89 strengthens antimicrobial defenses in bladder epithelial cells and, in combination with antibiotic therapy, limits post-antibiotic bacterial regrowth in epithelial infection models. OM-89 promotes lysosomal acidification and increases lysosomal protease activity in bladder organoids and differentiated epithelial monolayers, thereby directing intracellular UPEC toward degradative compartments. In parallel, OM-89 enhances intracellular accumulation of multiple antibiotic classes. These effects are conserved across distinct UPEC strains and in both murine and human epithelial models. Our findings demonstrate that bladder epithelial antimicrobial pathways can be pharmacologically reinforced to influence treatment outcomes by enhancing intracellular bacterial clearance.</p></div> 2026-09-25T17:25:06Z Dataset Dataset 10.1371/journal.ppat.1014448.t005 https://figshare.com/articles/dataset/_p_MICs_p_/33997963 CC BY 4.0