Home Biomedical research Cranberry Juice Won’t Enough: UTIs And The Potential For Drug Reuse |...

Cranberry Juice Won’t Enough: UTIs And The Potential For Drug Reuse | Science

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In May, doctoral students funded by the Medical Research Council (MRC) were invited to participate in the Max Perutz Prize for Scientific Writing 2021 and write a compelling article on their research for the non-scientific reader.

Among the many applications received, the 10 successful applicants covered a variety of topics including dementia, childhood adversity, the role of genes in schizophrenia and the use of hypnosis to treat psychosis.

The trials were judged by: the ObserverIan Tucker, Scientific Director of the Science Museum, Roger Highfield; Professor Fiona Watt, MRC Executive Chairman, Andy Ridgway, Senior Lecturer in Science Communication at the University of the West of England at Bristol, author and broadcaster Gaia Vince, and researcher and health advocate mental Dr Furaha Asani.

In a virtual ceremony last month, the £ 1,500 prize was presented to winner, Vicky Bennett of the University of Bath, for her article on her research into the reuse of drugs to treat urinary tract infections .

Here we publish the winning article, described by Roger Highfield as “a gallant way to make unglamorous research interesting”.

The winning essay

Vicky Bennett, author of the winning entry. Photograph: Courtesy of the Vicky Bennett / Max Perutz Prize

I am a biomedical research scientist. My lab essentials are a white coat, bubbling liquid, and the occasional blast. I make revolutionary discoveries every day. Crowds gather to marvel at my experiences and their vital implications.

At least that’s the impression my mother has of my doctorate so far.

The reality of my current situation seems somewhat different. My shiny white blouse was a wonderful addition to my wardrobe at first, but the many reservoirs of infected urine on my workbench are far from glamorous. (Actually, shiny white coat + infected urine = smelly yellow coat). Instead of crowds of admirers, the “little area” of our shared lab space is actively avoided. The consequences of any type of explosion are not worth considering.

Welcome to the world of urinary tract infection research.

Urinary tract infections (UTIs) are not particularly pleasant. They occur when the bacteria in poop come in contact with and enter the external opening of the urethra, the tube that allows urine to flow from the bladder to the outside of the body. If bacteria colonize the urethra, then they have direct access to the bladder. This is the ideal environment for them to multiply and spread upwards to infect the kidneys and even enter the bloodstream.

For those who are lucky enough not to have had a UTI, the frequent urge to urinate and a painful tingling or burning sensation when urinating are characteristic symptoms. UTIs are common at all ages, but obvious anatomical differences mean women suffer from them more frequently, as a shorter urethra reduces the distance bacteria must travel to reach the bladder. With up to 60% of adult women with at least one urinary tract infection in their lifetime (vs. 12% of men), many see them as an awkward but inevitable part of life. Data on the transgender experience of UTIs is limited, but counseling sites report that it can be a problem for genital tuckers and trans men taking testosterone. The victims even went so far as to describe their experiences in the form of songs. See Love song for my UTI by YouTuber Lex Croucher for one of my favorite examples.

A short course of antibiotics will eliminate most infections. But the number of bacteria resistant to antibiotics is increasing. Someone with an infection that was once curable within days can now try several different antibiotics before finding one that works. And even if your symptoms go away, the bacteria may not have been completely eradicated, with around 30% of infections reappearing within six months. Many people have to put up with a lifetime of recurring chronic UTIs and almost permanent symptoms.

Every UTI also has the risk of developing into a life-threatening kidney or blood infection. This risk increases with age and for people with underlying health conditions. The ever-growing threat of antibiotic resistance means that chronic and severe infections are increasingly common. Even the well-known mythical remedy of cranberry juice will have no effect against multidrug-resistant bacteria.

So the solution is to find new and better antibiotics, right? Something that quickly kills bacteria and makes it difficult for bacteria to become resistant to. This is essentially the objective of my thesis project. I’m trying to identify specific parts of bacteria that would be good targets for new antibiotics to attack. I will then use a computer modeling system to identify existing drugs that could be used in a new way to reach these targets and kill bacteria. These come from huge databases of millions of drugs used for all medical purposes, not necessarily existing antibiotics. This is a process called redirecting medication. If successful, this will reduce the time and costs associated with the development of new antibiotics.

This brings us back to my urine tanks. In my research group, we are working with a bacterium called Proteus mirabilis, a common cause of urinary tract infections associated with catheters (CAUTI). Urinary catheters are the most commonly used medical devices. The catheter is a long, flexible tube inserted through the urethra at the bottom of the bladder and is connected to a urine collection bag outside the body. They are used in people of all sexes with health problems that make it difficult for the bladder to empty naturally, as well as before or after certain types of surgery. Depending on the situation, the catheter can be temporary or permanent.

But the presence of a catheter facilitates the development of urinary tract infections. Bacteria grow much more easily on the surface of the catheter, and the tube allows them to enter directly into the urethra and bladder. As the bacteria build up, they will eventually block the tube and prevent urine from leaving the bladder. This causes urine to build up in the bladder, where it can flow back to the kidneys, increasing the risk of life-threatening kidney and blood infections, as well as causing tremendous pain due to the urinary retention itself.

We recreate this situation in the laboratory using catheters inserted into replicas of glass bladders. A pump system pushes urine through the bladder and into the catheter at body temperature so that we can monitor the effects of our experiences as realistically as possible. We infect the glass bladder and allow bacteria to grow on the surface of the catheter, where the buildup of bacteria will eventually block the tube and prevent urine from entering the collection bag.

A key aspect of these experiments is the reproducibility and reliability of the results. Actual urine varies widely depending on what someone has eaten or drunk, which is why I spend one day a week preparing five liter reservoirs of artificial urine to use in my experiments to ensure consistency. . It involves mixing water with urea and various salts such as potassium and sodium chloride. It even smells like the real thing.

The time it takes to block the catheter determines the success of different drugs. These can be tested in several ways: either by being flushed into the bladder through the catheter, dissolved in the urine, or applied as a coating to the catheter before it is inserted. The longer the catheter blocking time, the more promising the treatment. And you wouldn’t believe the anticipation and excitement of watching urine slowly flow through a bacteria-encrusted catheter.

Of course, I haven’t got 12 months into my three-and-a-half-year plan yet, and there’s a long, long way to go before handing a patient medication that will cure their infection. However, I really hope that my research will support the development of new antibiotic treatments to help patients with ICAU, chronic UTIs not treatable with existing medications, and anyone who is fed up with that burning sensation when it comes to it. go pee.


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