BioTechniques News
Maddy Chapman
Phages could be the answer to wiping out persistent UTIs, as demonstrated by a new flow-enabled bladder model.
A team led by researchers at University College London (UK) has integrated a novel fluidic platform with a 3D micro-bladder model to more closely mimic the human bladder, offering a more representative environment for testing urinary tract infection (UTI) drugs. The new technology provides insight into why UTIs return so frequently, in addition to highlighting the efficacy of phage therapy against UTI bacteria.
Like so much early-stage research that has potential for benefiting human health, the models being used and developed play a major role in the process, whether that be identifying novel drug targets or developing new drugs. If the model system isn’t similar to the biological conditions of the system of interest, you can be pretty sure the work won’t translate as smoothly as one would hope. For example, when scientists test drugs against the bacteria found in urine samples, those drugs might perform wonderfully but give them to a person, and they might not clear the entire infection.
This is a significant problem for UTIs, which often come back after being treated with antibiotics due to a growing antimicrobial resistance issue. To understand the mechanisms by which UTIs recur, a recent study used a 3D human urothelial microtissue model and a novel fluidic platform that mimics urine flow dynamics to study infection caused by uropathogenic Escherichia coli (UPEC), the microbe responsible for most UTIs.
The team found that UPEC was far more infective in the physiologically relevant, flow-enabled bladder models than in traditional still lab tests, with bacteria infiltrating the bladder lining and forming bacterial reservoirs within the bladder, which likely explains why UTI recurrence is so common.
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Next, the team tested the efficacy of common UTI antibiotics in both a standard in vitro antimicrobial susceptibility test and the flow-augmented bladder model. They found that nitrofurantoin, a first-line UTI drug, was less effective in the bladder model, while working well in the standard test.
Finally, the team tried treating the microtissue model with a cocktail of bacteriophages – viruses that target bacteria, which have gained positive momentum in the fight against antimicrobial resistance – in isolation and in conjunction with nitrofurantoin. The phages on their own could not fully clear the infection, but as a combination therapy, the drugs were effective in the urinary microenvironment, demonstrating a promising treatment option for UTIs.
“By combining a realistic flowing micro-bladder model with phage and antibiotic treatment, we can begin to understand how best to use phages alongside existing medicines to achieve better outcomes for patients,” commented Martha Clokie, Director of the Becky Mayer Centre for Phage Research at the University of Leicester (UK).
Although not totally effective in isolation, the phages were able to reduce the number of bacterial reservoirs within the bladder lining – areas that serve as breeding grounds for bacteria and are therefore key to recurrent infections. They were also found to induce inflammatory cytokine and chemokine secretion. Given these promising findings, phages – in combination with antibiotics – may well become treatment options for recurrent UTIs; however, more research is necessary before these bacterial viruses make their way into the clinic.
The post Could bacteriophages put an end to recurrent UTIs? appeared first on BioTechniques.
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