Urinary tract infections (UTIs) are among the most common bacterial infections, frequently caused by Escherichia coli. But UTIs are known to be recurrent, even after antibiotic treatment. One reason is that the bacterium can enter the cells of the bladder epithelium to evade both antibiotics and the patient’s immune system, and re-emerge. Researchers have now identified a way to strengthen the bladder cells’ own ability to eliminate these hidden bacteria.
The study, published in PLOS Pathogens, is entitled, “Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli.”
The findings suggest that the drug OM-89 (marketed as Uro-Vaxom®) activates cellular degradation pathways in bladder epithelial cells while also increasing antibiotic uptake. OM-89 has been used for decades to help prevent recurrent UTIs. It is mainly known for stimulating the immune system, but the new study reveals a second mechanism of action: a direct effect on the cells lining the bladder.
The researchers studied mouse and human bladder epithelial cells using organoid models and differentiated cell cultures. They exposed the cells to OM-89, infected them with different strains of E. coli, and treated them with antibiotics. They then tracked bacterial survival, antibiotic uptake, and changes in cellular pathways involved in destroying intracellular material.
The findings show that OM-89 increased lysosomal acidification as well as the activity of lysosomal enzymes. When the researchers blocked lysosomal acidification, OM-89’s protective effect was lost, suggesting that lysosomal activity is directly involved in reducing bacterial regrowth in recurrent UTIs. In addition, OM-89 increased the accumulation of antibiotics inside bladder epithelial cells—an effect that extended across different antibiotic classes and several bacterial strains, including clinical samples from patients.
“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 findings point toward a host-directed approach to recurrent infection: rather than targeting bacteria alone, treatment could also reinforce the antimicrobial machinery of the infected tissue itself.
More broadly, the study identifies lysosomal pathways in the bladder epithelium as a potential target for future treatment combinations designed to improve antibiotic outcomes.
“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,” adds Christian Pasquali, senior scientific liaison director at OM Pharma and former head of preclinical research.