(Press-News.org) The research, published today in Science Advances, is the first to use a sophisticated human tissue model to explore the interaction between host and pathogen for six common species that cause urinary tract infections. The findings suggest that the ‘one size fits all’ approach to diagnosis and treatment currently used in most healthcare systems is inadequate.
Urinary tract infection (UTI) is 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 UTI is often perceived as a simple bacterial infection, 25-30% of UTIs recur within six months despite antibiotic therapy for reasons that are poorly understood.
A condition that primarily affects women, UTI has been historically understudied and underfunded, with no improved anti-infective treatments introduced since Alexander Fleming discovered antibiotics nearly a century ago. Diagnosis primarily rests on the midstream urine culture method (dipstick test), an early 20th century technique that is known to miss many infections.
In this study, researchers from UCL developed three-dimensional cell models capable of mimicking the biological environment and function of human bladder tissue, in order to observe the interactions between host and pathogen in conditions as close to the human body as possible1. These ‘mini bladders’ 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, senior author of the study from UCL Division of Medicine, 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. 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, which means you live 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 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. All the ‘bad’ bugs tested triggered the production of immune molecules, called cytokines, and the shedding of the top layer of the bladder wall, whereas the ‘good’ bacteria could colonise the bladder wall without triggering an immune response.
Dr Carlos Flores, first author of the study from UCL Division of Medicine, 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.”
The findings indicate that effective treatments for persistent UTIs may require the ability to penetrate human tissues, in order to reach bacterial populations dwelling in the bladder wall. A UCL spin-out, AtoCap, is currently developing ways to deliver drugs inside cells to target pathogens hiding there.
Professor Rohn concluded: “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. Not all bugs can be cultured in the lab, and even if they could be that doesn’t tell us if this strain is the cause of an infection or if its position in the bladder wall would make the standard three-day course of antibiotics unlikely to eradicate it.”
Helen Lucas, a patient from Hertfordshire who has struggled with chronic UTIs for several years, said: “Before my UTI problem started, I just assumed that living in the UK you could go to your doctor, be prescribed treatment and get better. It’s been a shock to find that the testing and treatment of UTIs, even the perceptions of what this disease can be, are so antiquated.
“If I wasn’t outspoken, I think might have been left with an undiagnosed chronic UTI, unable to fully live my life. I know other people are struggling to overcome the same hurdles that I had to. It’s fantastic that research is being done into why UTIs persist, which will hopefully lead to better testing and treatment.”
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.”
Notes to Editors:
For more information or to speak to someone who has experienced a UTI for comment on the findings, please contact:
Dr Matt Midgley
+44 (0)20 7679 9064
m.midgley@ucl.ac.uk
1 The mini bladders used in the study are currently the most sophisticated artificial bladder models in the world. About the size of a five-pence coin (UK) or a dime (US), the models are grown in plastic dishes bathed in human urine. Unlike other models, the mini bladders have 7-8 layers to resemble the structure of the human bladder and can operate in 100% urine, a toxic environment that is the natural habitat of UTI bugs. They include lifelike human features such as a mucous-like barrier that separates the bladder wall from urine and the ability to emit immune distress signals when attacked.
Publication:
Carlos Flores et al. ‘A human urothelial microtissue model reveals shared colonization and 4 survival strategies between uropathogens and commensals’ will be published in Science Advances and is strictly embargoed until Wednesday 8 November 19:00 GMT / 14:00 ET.
DOI: https://doi.org/10.1126/sciadv.adi9834
About UCL – London’s Global University
UCL is a diverse global community of world-class academics, students, industry links, external partners, and alumni. Our powerful collective of individuals and institutions work together to explore new possibilities.
Since 1826, we have championed independent thought by attracting and nurturing the world's best minds. Our community of more than 50,000 students from 150 countries and over 16,000 staff pursues academic excellence, breaks boundaries and makes a positive impact on real world problems.
The Times and Sunday Times University of the Year 2024, we are consistently ranked among the top 10 universities in the world and are one of only a handful of institutions rated as having the strongest academic reputation and the broadest research impact.
We have a progressive and integrated approach to our teaching and research – championing innovation, creativity and cross-disciplinary working. We teach our students how to think, not what to think, and see them as partners, collaborators and contributors.
For almost 200 years, we are proud to have opened higher education to students from a wide range of backgrounds and to change the way we create and share knowledge.
We were the first in England to welcome women to university education and that courageous attitude and disruptive spirit is still alive today. We are UCL.
www.ucl.ac.uk | Follow @uclnews on Twitter | Read news at www.ucl.ac.uk/news/ | Listen to UCL podcasts on SoundCloud | View images on Flickr | Find out what’s on at UCL Mind
END
Artificial bladders shine light on bugs that cause urinary tract infections
2023-11-08
ELSE PRESS RELEASES FROM THIS DATE:
Temperature increase triggers the viral infection
2023-11-08
Researchers at Lund University, together with colleagues at the NIST Synchrotron Facility in the USA, have mapped on an atomic level what happens in a virus particle when the temperature is raised.
"When the temperature rises, the virus's genetic material changes its form and density, becoming more fluid-like, which leads to its rapid injection into the cell," says Alex Evilevitch a researcher at Lund University who led the study.
Viruses lack their own metabolism and the ability to replicate independently; they are entirely dependent on a host cell to multiply. Instead, the virus hijacks the internal machinery of the infected cell ...
Molecule tested at University of São Paulo, in Brazil, proves able to mitigate heart failure
2023-11-08
Researchers at the University of São Paulo (USP) in Brazil, partnering with Foresee Pharmaceuticals, a Taiwan and US-based biopharmaceutical company, have tested a synthetic molecule for the treatment of heart failure. The study, funded by FAPESP, was published yesterday (11/07/2023) in the European Heart Journal. The theme was also highlighted in the magazine's editorial.
Heart failure is a condition in which the heart muscle cannot pump enough blood to meet the body's needs for blood and oxygen. It causes more deaths worldwide than any other disease, in the sense that other cardiovascular disorders ...
How mice choose to eat or to drink
2023-11-08
Making decisions is hard. Even when we know what we want, our choice often leaves something else on the table. For a hungry mouse, every morsel counts. But what if the decision is more consequential than choosing between crumbs and cheese?
Stanford researchers investigated how mice resolve conflicts between basic needs in a study published in Nature on Nov. 8. They presented mice that were both hungry and thirsty with equal access to food and water and watched to see what happened next.
The behavior of the mice surprised the scientists. Some gravitated first ...
Plant lifecycle insights: Big data can predict climate change impact
2023-11-08
The study is based on a new database created by the researchers which combines, for the first time, datasets on distribution and datasets on lifecycles, making it possible to establish the prevalence of different lifecycles around the globe. It uses empirical tools and big data to examine theoretical paradigms about the way in which human disturbance is affecting annual plants and their global distribution. Among other things, it was found that annuals are expected to benefit more with the rise in human population density and due to climate change, which ...
Scientists one step closer to re-writing world’s first synthetic yeast genome, unravelling the fundamental building blocks of life
2023-11-08
Scientists have engineered a chromosome entirely from scratch that will contribute to the production of the world’s first synthetic yeast.
Researchers in the Manchester Institute of Biotechnology (MIB) at The University of Manchester have created the tRNA Neochromosome – a chromosome that is new to nature.
It forms part of a wider project (Sc2.0) that has now successfully synthesised all 16 native chromosomes in Saccharomyces cerevisiae, common baker’s yeast, and aims to combine ...
Scientists take major step towards completing the world’s first synthetic yeast.
2023-11-08
A UK-based team of Scientists, led by experts from the University of Nottingham and Imperial College London, have completed construction of a synthetic chromosome as part of a major international project to build the world’s first synthetic yeast genome.
The work, which is published in Cell Genomics, represents completion of one of the 16 chromosomes of the yeast genome by the UK team, which is part of the biggest project ever in synthetic biology; the international synthetic yeast genome collaboration.
The collaboration, known as 'Sc2.0' has been a 15-year project involving teams from around the world (UK, US, China, Singapore, UK, France and Australia), working together ...
New antifungal molecule kills fungi without toxicity in human cells, mice
2023-11-08
CHAMPAIGN, Ill. — A new antifungal molecule, devised by tweaking the structure of prominent antifungal drug Amphotericin B, has the potential to harness the drug’s power against fungal infections while doing away with its toxicity, researchers at the University of Illinois Urbana-Champaign and collaborators at the University of Wisconsin-Madison report in the journal Nature.
Amphotericin B, a naturally occurring small molecule produced by bacteria, is a drug used as a last resort to treat fungal infections. While AmB excels at killing fungi, it is reserved ...
Cellular “atlas” built to guide precision medicine treatment of rheumatoid arthritis
2023-11-08
Research consortium investigators analyzed over 314,000 cells from rheumatoid arthritis tissue, defining six types of inflammation involving diverse cell types and disease pathways
Understanding the disease at single-cell level may advance targeted drug development and treatment strategies
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple ...
Estimated effectiveness of co-administration of the Pfizer-BioNTech COVID-19 vaccine with influenza vaccine
2023-11-08
About The Study: In this study that included 3.4 million adults, co-administration of the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (Pfizer-BioNTech) and seasonal influenza vaccine was associated with generally similar effectiveness in the community setting against COVID-19–related and seasonal influenza vaccine-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.
Authors: Leah J. McGrath, Ph.D., of Pfizer Inc., in New York, is the corresponding author.
To ...
Age at diagnosis of atrial fibrillation and incident dementia
2023-11-08
About The Study: Earlier onset of atrial fibrillation was associated with an elevated risk of subsequent all-cause dementia, Alzheimer disease, and vascular dementia in this study including 433,000 UK Biobank participants, highlighting the importance of monitoring cognitive function among patients with atrial fibrillation, especially those younger than 65 years at diagnosis.
Authors: Fanfan Zheng, Ph.D., of the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, and Wuxiang Xie, Ph.D., of the Peking University First ...