Epithelial Reprogramming by OM-89 Enhances Antibiotic Clearance of Uropathogenic E. coli in a Bladder Organoid Model
Tomasek, K.; Skurvydaite, K.; Paduthol, G.; Burns, A. M.; Schlunke, L.; Pasquali, C.; Romani, M.; McKinney, J. D.
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Recurrent urinary tract infections (UTIs) are a major clinical burden, driven by the ability of uropathogenic Escherichia coli (UPEC) to persist intracellularly. While vaccine and antibiotic alternatives are being explored, strategies that enhance epithelial cell-intrinsic defenses remain limited. Here, we show that OM-89 (Uro-Vaxom(R)), an E. coli lysate, reprograms epithelial antimicrobial responses to enhance intracellular bacterial clearance. Using murine bladder organoids and epithelial monolayers, we demonstrate that OM-89 increases lysosomal acidification and cathepsin activity, promoting trafficking of UPEC into degradative compartments. Unexpectedly, OM-89 also increases epithelial uptake of antibiotics, boosting their intracellular potency and reducing UPEC regrowth after treatment. This dual effect on epithelial immunity and antibiotic accessibility was conserved across multiple UPEC strains and antibiotic classes. These findings position bladder epithelial cells as active players in the host defense and highlight OM-89 as a tool to amplify their antimicrobial potential, offering a promising adjunctive strategy against intracellular bacterial persistence.
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