<p>MICs.</p>

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.