A drug used for decades to prevent recurrent urinary tract infections does more than stimulate the immune system: researchers at EPFL report in PLOS Pathogens that OM-89 (Uro-Vaxom®) directly activates degradation pathways inside bladder epithelial cells and increases intracellular antibiotic accumulation, curbing regrowth of uropathogenic Escherichia coli after treatment stops.

The finding matters for a persistent clinical problem. UTIs rank among the most common bacterial infections, and E. coli drives most of them. Infections recur even after antibiotic courses because the bacterium slips inside bladder epithelium cells, sheltering from both antibiotics and immune attack, then re-emerges. The study, titled "Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli," points to the host cell — not just the pathogen — as a druggable target.

The team worked with mouse and human bladder epithelial cells in organoid models and differentiated cell cultures. They exposed cells to OM-89, infected them with several E. coli strains — including clinical isolates from patients — treated them with antibiotics, and tracked bacterial survival, antibiotic uptake, and changes in the cellular machinery that destroys intracellular material.

Two results stand out. First, OM-89 increased lysosomal acidification and the activity of lysosomal enzymes, the cell's internal degradation system. When the researchers blocked lysosomal acidification, the protective effect disappeared — direct evidence that lysosomal activity drives the reduction in bacterial regrowth rather than a bystander effect. Second, OM-89 raised antibiotic accumulation inside bladder epithelial cells, and this effect held across different antibiotic classes and multiple bacterial strains, including the clinical samples.

"We found that OM-89 doesn't just stimulate the innate immune system as previously assumed," says Kathrin Tomasek, PhD, project leader at the Laboratory of Microbiology and Microtechnology at EPFL. "It acts directly on bladder cells, strengthening their degradation pathways so they can destroy hidden bacteria more effectively while also helping antibiotics reach those bacteria — together reducing regrowth of the bacteria after treatment ends."

The study carries an industry connection that readers should weigh. Christian Pasquali, senior scientific liaison director at OM Pharma — the company marketing Uro-Vaxom® — and former head of preclinical research, co-authored the commentary on the work. His statement frames the results carefully: "While the results come from preclinical models and do not change the approved indication or use of Uro-Vaxom®, they deepen our understanding of how OM-89 may help strengthen the bladder's natural defenses against recurrent infection and reinforce the scientific foundation supporting its use."

That caveat is worth keeping in view. The data come from organoids and differentiated cultures, not from controlled trials in patients. The paper does not report effect sizes from human clinical endpoints, and the mechanism, while demonstrated in human-derived cells, remains to be confirmed in infected tissue in vivo.

Even with those limits, the strategic implication for R&D portfolios is clear. Rather than targeting bacteria alone — a strategy under pressure from resistance — the work validates a host-directed approach: reinforcing the antimicrobial machinery of the infected tissue itself. The study explicitly identifies lysosomal pathways in bladder epithelium as a potential target for future combination treatments designed to improve antibiotic outcomes, which could extend the useful life of existing antibiotic classes.

For groups building programs in anti-infectives or host-directed therapeutics, the next questions are translational: whether lysosomal activation measurably reduces recurrence rates in patients, and whether the antibiotic-uptake effect scales in vivo. The EPFL team's mechanistic framework gives clinical investigators a defined pathway to test.