Human Urothelial Microtissue Model Illuminates Host-Uropathogen Interactions in UTIs

University College London researchers employed sophisticated human tissue models to investigate interactions between hosts and pathogens responsible for urinary tract infections (UTIs). The findings, published in Science Advances, challenge the conventional "one size fits all" approach to UTI diagnosis and treatment, shedding light on the complexities of this common ailment.

Urinary tract infections are a global health concern, with approximately 400 million cases reported annually, and an alarming 250,000 UTI-related deaths linked to antimicrobial resistance. While UTIs are often perceived as straightforward bacterial infections, an unsettling 25-30% of cases reoccur within six months, despite antibiotic treatment.

Historically, UTIs have been under-researched and underfunded, primarily affecting women. Astonishingly, no significant advances in anti-infective treatments have emerged since the discovery of antibiotics by Alexander Fleming nearly a century ago. The standard method for diagnosis relies on the midstream urine culture (dipstick test), a century-old technique notorious for missing many infections.

In this investigation, UCL scientists developed three-dimensional cell models that accurately mimic the biological environment and function of human bladder tissue. These "mini bladders" were exposed to six common bacterial species found in human bladders, including Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae, and Klebsiella pneumoniae.

Jennifer Rohn, the study's senior author, noted the diversity of behaviors exhibited by different UTI bacteria. One key observation was the importance of bacterial persistence. Pathogens that can evade treatment and immune defenses tend to thrive. Some bacterial species, both benign and pathogenic, formed protective pods within the bladder wall. While this aids friendly bacteria, it poses significant problems for diagnosis and treatment when a harmful infection is present, as these bacteria may remain undetected in urine samples and out of reach for oral antibiotics.

The study also highlighted that human cells can effectively differentiate between benign and harmful bacteria, regardless of their ability to infiltrate the bladder wall. "Bad" bacteria triggered the production of immune molecules and the shedding of the bladder's top layer, while "good" bacteria could colonize the bladder wall without eliciting an immune response.

Carlos Flores, the study's first author, suggested that next-generation UTI diagnostics could focus on identifying harmful bacteria based on the body's immune response rather than trying to detect them amidst the background noise of the microbiome.