Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli
- 1Laboratory of Microbiology and Microtechnology, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- 2Bioinformatics Competence Centre, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- 3OM Pharma Ltd., Meyrin/Geneva, Switzerland
Abstract
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. Author summary: Urinary tract infections are common, and for many people recur after antibiotic treatment appears to succeed. This happens partly because some bacteria survive treatment hidden inside the cells lining the bladder, allowing infection to return once treatment stops. OM-89, an orally-given bacterial lysate already used to prevent recurrent infections, is thought to work mainly by stimulating the immune system, but whether it also acts directly on bladder cells has been unclear. Using bladder organoids and cell models from both mice and humans, we show that OM-89 strengthens the bladder’s own antibacterial defenses. It boosts the activity of lysosomes, the cellular compartments degrading harmful material, helping infected cells destroy bacteria more effectively. OM-89 also increased how much antibiotic entered bladder cells. Together, these effects improved bacterial clearance and reduced regrowth after antibiotic treatment. This protective effect held across multiple bacterial strains and in cell models from both mice and humans, and the underlying pathway is linked to natural immune defense activity in independent human bladder tissue datasets, supporting its relevance beyond our own models. Our findings offer a possible cellular explanation for how OM-89 helps prevent recurrent urinary tract infections and point toward more effective antibiotic treatment against this common infection.
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BibTeX
@article{tomasek2026targeted,
title = {{Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli}},
author = {Kathrin Tomasek and Kristina Skurvydaite and Gauri Paduthol and Allison M. Burns and Léa Schlunke and Valentin Borgeat and Christian Pasquali and Mario Romani and John D. McKinney},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014448},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014448},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli
AU - Kathrin Tomasek
AU - Kristina Skurvydaite
AU - Gauri Paduthol
AU - Allison M. Burns
AU - Léa Schlunke
AU - Valentin Borgeat
AU - Christian Pasquali
AU - Mario Romani
AU - John D. McKinney
PY - 2026
DA - 2026/09/25
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014448
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014448
AB - 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. Author summary: Urinary tract infections are common, and for many people recur after antibiotic treatment appears to succeed. This happens partly because some bacteria survive treatment hidden inside the cells lining the bladder, allowing infection to return once treatment stops. OM-89, an orally-given bacterial lysate already used to prevent recurrent infections, is thought to work mainly by stimulating the immune system, but whether it also acts directly on bladder cells has been unclear. Using bladder organoids and cell models from both mice and humans, we show that OM-89 strengthens the bladder’s own antibacterial defenses. It boosts the activity of lysosomes, the cellular compartments degrading harmful material, helping infected cells destroy bacteria more effectively. OM-89 also increased how much antibiotic entered bladder cells. Together, these effects improved bacterial clearance and reduced regrowth after antibiotic treatment. This protective effect held across multiple bacterial strains and in cell models from both mice and humans, and the underlying pathway is linked to natural immune defense activity in independent human bladder tissue datasets, supporting its relevance beyond our own models. Our findings offer a possible cellular explanation for how OM-89 helps prevent recurrent urinary tract infections and point toward more effective antibiotic treatment against this common infection.
SN - 1553-7374
ER -