Health UK (Commonwealth Union) – A recent research project led by the University College London (UCL) scientists has unveiled a fascinating revelation: multiple strains of bacteria possess the ability to conceal themselves within the human bladder wall. This discovery sheds light on why urinary tract infections (UTIs) often linger even after treatment.
The study, which was featured in the latest issue of Science Advances, marks the first-time researchers have employed an advanced human tissue model to investigate the interplay between the human host and six prevalent bacterial species responsible for UTIs. These results call into question the current ‘one-size-fits-all’ approach to diagnosing and treating UTIs, which is commonly employed in most healthcare systems.
UTIs have become a growing concern, affecting roughly 400 million people worldwide each year and contributing to an estimated 250,000 deaths linked to antimicrobial resistance (AMR). Despite being generally viewed as a straightforward bacterial infection, 25-30% of UTIs recur within 6 months, even with antibiotic treatment, for reasons that have not been clearly known.
Primarily impacting women, UTIs have been historically neglected and underfunded, with no significant advancements in anti-infective treatments since the discovery of antibiotics by Alexander Fleming nearly a century ago. Diagnosis is primarily reliant on outdated methods, such as the midstream urine culture (dipstick test), a technique from the early 20th century that is known to miss many infections.
In this groundbreaking study, UCL researchers developed three-dimensional cell models that could accurately replicate the biological environment and function of human bladder tissue. This permitted them to monitor the interactions between the host and pathogens in conditions closely resembling the human body. These miniature bladder models were exposed to six bacterial species commonly found in the human bladder: Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae, and Klebsiella pneumoniae.
Professor Jennifer Rohn, the senior author of the study from UCL’s Division of Medicine, expressing views on their findings, indicated that we are subjected various UTI bacterial species and strains to rigorous examination and uncovered a dynamic battleground of diversity. One of our most significant observations highlighted the importance of persistence. To be an effective pathogen, it’s essential to employ strategies that enable survival through treatment and evasion of vigilant immune cells, ensuring the pathogen lives to fight another day.
“Some species of both ‘good’ and ‘bad’ bugs formed pods within the bladder wall, most likely as a way of surviving in this harsh environment. If this happens with a friendly bug, this isn’t a problem. But if the bug is causing an infection, this poses a serious problem for diagnosis and treatment because the bacteria aren’t necessarily going to be detected in a urine sample or be in a position where oral antibiotics can reach them.”
The study also revealed that human cells possess a remarkable capacity to discern between friendly and unfriendly bacteria, irrespective of their ability to invade the bladder wall. All the tested ‘harmful’ bacteria triggered the release of immune molecules known as cytokines and caused the shedding of the bladder wall’s outer layer. In contrast, the ‘beneficial’ bacteria could establish themselves on the bladder wall without eliciting an immune response.
Dr. Carlos Flores, the lead researcher from the Division of Medicine at UCL, suggested that the study’s results pave the way for a new approach to UTI diagnostics. Rather than trying to detect troublesome bacteria in the midst of the diverse microbiome, the next generation of UTI diagnostics could focus on identifying ‘problematic’ bacteria based on the body’s immune response. While the human bladder houses a wide range of bacterial species and strains that are not fully understood, the body appears to have a remarkable ability to differentiate between friendly and harmful microbes.
These discoveries suggest that effective treatments for persistent UTIs might necessitate the ability to penetrate human tissues to target bacterial populations concealed within the bladder wall. A UCL-affiliated venture, AtoCap, is presently exploring strategies to deliver drugs inside cells to specifically target these hidden pathogens.
