Phages reach hidden UTI bacteria in a lab-grown bladder

At Professor Jennifer Rohn’s laboratory at UCL’s Division of Medicine, a pipette hovers over a human 3D micro-bladder designed to carry flowing urine. In the model, researchers from UCL, the University of Oxford and the University of Leicester found that phages could reduce UTI bacteria hidden inside the bladder wall—protected reservoirs that antibiotics struggled to clear.

Urinary tract infections are among the world’s most common infections, with around 400 million cases each year. They can return after a course of antibiotics because the bacteria are not always gone: some can survive inside the bladder lining, where they are harder for treatment to reach. The team focused on uropathogenic Escherichia coli, or UPEC, a strain adapted to infect the urinary tract and the cause of most UTIs.

The model was built to correct a blind spot in routine testing. Hospital laboratories commonly test a patient’s bacteria in still, nutrient-rich liquid, while a real bladder has urine flow and a living lining. Dr. Ramon Garcia Maset and colleagues at Oxford developed a device that works with typical cell cultures to recreate the flow conditions of urinary cycles. When UPEC was introduced, it became better at sticking to the bladder surface, invading the lining and forming reservoirs inside bladder cells. Nitrofurantoin worked well in standard tests but struggled to fully clear the infection in the micro-bladder.

The researchers then tested a phage cocktail—viruses that infect and destroy bacteria. In the flowing model, phages alone also struggled to clear the infection. Combined with the antibiotic, however, treatment results improved. The distinction was in the reservoirs: unlike the antibiotic, phages reduced the number of protected bacterial reservoirs inside the bladder wall. The team also saw signs of increased immune signaling, including cytokines and chemokines, messenger proteins that help coordinate inflammation and bring immune cells to an infection.

So what changes, concretely? Doctors do not yet have a routine phage treatment for recurrent UTIs, but laboratories now have a model that may reveal why a drug appears effective in a standard test and fails against bacteria sheltered in bladder tissue. The study’s results come from a lab-grown model, and further research is needed to confirm effectiveness, determine how to deliver phages and identify which patients are most likely to benefit. The device design and image-analysis tools are freely available to other laboratories.