Numerous bacterial strains are capable of hiding in the human bladder wall, suggesting why urinary tract infections (UTIs) often persist after treatment, according to UK researchers.
Their study is the first to use a sophisticated human tissue model to explore the interaction between host and pathogen for six common species that cause UTIs.
“We put a variety of UTI bacteria species and strains through their paces and discovered a battleground of diversity”
The findings, published this week in the journal Science Advances, suggest that the ‘one size fits all’ approach to diagnosis and treatment currently used in most healthcare systems is inadequate.
UTIs are a growing problem, with around 400 million global cases per year and an estimated 250,000 UTI-related deaths associated with antimicrobial resistance (AMR).
Although UTIs are often perceived as a simple bacterial infection, 25-30% of them recur within six months, despite antibiotic therapy, for reasons that are poorly understood, noted the researchers.
They also suggested that UTI has been historically understudied, with no improved anti-infective treatments introduced since Alexander Fleming discovered antibiotics nearly a century ago.
In addition, they noted that diagnosis primarily rested on the midstream urine culture method – the dipstick test – an early 20th century technique that is known to miss many infections.
The researchers, from University College London, developed three-dimensional cell models, or ‘mini bladders’, capable of mimicking the biological environment and function of human bladder tissue.
They did this in order to observe the interactions between host and pathogen in conditions as close to the human body as possible.
The ‘mini bladders’ were exposed to six commonly-found bacterial species – Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae and Klebsiella pneumoniae.
Professor Jennifer Rohn, senior author of the study, said: “We put a variety of UTI bacteria species and strains through their paces and discovered a battleground of diversity.
“One of the key observations was the importance of persistence,” she said. “If you want to be a successful pathogen, you have to have strategies that help you to survive treatment and hide from patrolling immune cells.
“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,” she noted.
The study also found that human cells were very good at distinguishing friendly from not-so-friendly bacteria, regardless of whether they could invade the bladder wall or not.
“Professor Rohn’s work in this field is a vitally important step forwards”
All the ‘bad’ bugs triggered the production of immune molecules, cytokines, and the shedding of the top layer of the bladder wall, whereas the ‘good’ bacteria could colonise the wall without triggering a response.
Dr Carlos Flores, first author of the study, said: “Based on our results, next-generation diagnostics for UTIs could focus on identifying ‘bad’ bugs based on how the body responds, rather than trying to spot the presence of problem bacteria among the background noise of the microbiome.
“There are so many species and strains of bacteria in the human bladder that we don’t fully understand, but the body seems to be pretty good at telling friend from foe,” he noted.
Professor Rohn added: “This study confirms what many women who’ve struggled with persistent UTIs already know, which is that the current methods of diagnosing and treating these infections are inadequate.
“Urine dipstick tests are too likely to miss infections hiding in the bladder wall, especially when a patient’s first response to discomfort is to drinks lots of water, which dilutes the test,” she said.
Carolyn Andrew, director of the Chronic Urinary Tract Infection Campaign (CUTIC), said: “This research has been instrumental in providing unequivocal evidence for our national campaign to improve testing and diagnosis of chronic, persistent UTIs.
“Professor Rohn’s work in this field is a vitally important step forwards and should help tens of thousands of women in the UK to receive effective diagnosis and treatment of a chronic infection in their bladders.”