Cranberry juice won’t cut it: UTIs and the potential for repurposing drugs

PhD students funded by the Medical Research Council (MRC), were invited to submit compelling pieces about their research to the Max Perutz science writing prize 2021.
The 10 shortlisted entries were a mix of topics such as dementia, childhood adversity and the role of genes for schizophrenia.

The essays were judged: by the Observers Ian Tucker and Roger Highfield, Science Museums science director; Prof Fiona Watt and Andy Ridgway. Senior lecturer in science communication at the University of the West of England, Bristol. Gaia Vince was the author. Dr Furaha Asani is a researcher and mental health advocate.

Vicky Bennett, University of Bath, was awarded the 1,500 prize at a virtual ceremony for her article on repurposing drugs that can be used to treat infections of the urinary tract.

Roger Highfield describes the winning article as "a gallant way of making unglamorous research interesting".

The winner essay

Vicky Bennett is the author of this winning entry. Photo: Vicky Bennett/Max Perutz prize

I am a biomedical researcher scientist. My lab essentials include a white lab coat, bubbling liquid and occasional explosion. Every day I discover new things. My experiments are admired by many people who want to save their lives.

At least, this is my mum's impression of my PhD thus far.

My current reality is somewhat different. Although my shiny white lab coat was a great addition to my wardrobe, the numerous tanks of infected urine at my workbench were not glamorous. Shiny white lab coat + infected blood = yellow lab coat. Instead of admirers in large numbers, we actively avoid the small area of shared lab space. Any kind of explosion can have devastating consequences that are hard to imagine.

Welcome to the world urinary tract infection research.

UTIs (urinary tract infections) can be very unpleasant. These infections occur when bacteria from poo comes into contact with the bladder's external opening, which allows urine to flow to the outside. If bacteria colonizes the urethra they have direct access to your bladder. This environment is ideal for bacteria to grow and spread upwards to infect kidneys or enter bloodstream.

UTI symptoms include a burning sensation or stinging sensation in the urine and an urge to urinate. UTIs can occur at any age, although they are more common in women than men. Because of the shorter length of the urethra, bacteria travels less distance to reach the bladder. UTIs are a common problem in adult women, with 60% experiencing at least one UTI during their lives (compared to just 12% for men). Many view them as an uncomfortable but necessary part of everyday life. Although data on transgender UTIs is scarce, advice sites state that they can be a problem for transgender men who are taking testosterone and genital tuckers. Some sufferers even went so far as singing about their experiences. For one of my favorite examples, see Love song for UTI by Lex Croucher on YouTube.

Most infections can be treated with a short course of antibiotics. However, the number of bacteria that are resistant to antibiotics continues to rise. A person with an infection that was once treatable within a few days might now need to try multiple antibiotics before they find one that works. Even if you feel better, there is a chance that your symptoms will return within six months. Many people have to accept the fact that they will experience recurring UTIs for life.

UTIs can also lead to a potentially life-threatening infection such as a bloodstream or kidney infection. The risk of developing a life-threatening kidney infection or bloodstream infection increases with age and for people with existing health conditions. Chronic and severe infections are increasing due to antibiotic resistance. Multidrug-resistant bacteria will not be treated with cranberry juice, a well-known mythical remedy.

The solution is to find better antibiotics. You need something that kills bacteria quickly, and is difficult for bacteria to resist. My PhD project aims to achieve this end. I'm trying to find specific bacteria parts that could be targeted for new antibiotics. The computer modeling system will allow me to identify drugs that could be used to kill these bacteria targets. These drugs come from vast databases that contain millions of drugs, which can be used for any purpose in medicine. This is known as drug repurposing. It will help reduce the cost and time involved in developing new antibiotics.

Each week, I make five-litre tanks of artificial urine to be used in my experiments.

We are now back at my urine tanks. My research group works with Proteus mirabilis bacteria, which is a common cause for catheter-associated urinary tract infection (CAUTIs). The most common medical device is the urinary catheter. The catheter is a flexible tube that is inserted through the urethra and into the bottom bladder. It is then connected to a bag outside the body for urine collection. These catheters are useful for people of all ages with medical conditions that make it difficult for the bladder to empty naturally. They can also be used before and after certain types of surgery. The catheter can be temporary or permanent, depending on the circumstances.

UTIs can be prevented by the use of a catheter. The catheter's surface allows bacteria to grow more quickly, and the tube gives them a direct route to the bladder and urethra. The bacteria builds up and eventually blocks the tube, preventing urine from leaving the bladder. The urine can collect in the bladder and flow backwards to the kidneys. This increases the risk of serious kidney and bloodstream infections.

This is how we recreate the situation in our lab using catheters that are inserted into glass bladders. The bladder is heated to allow urine to flow through the catheter. This allows us monitor the results of our experiments and ensures that they are as real-life as possible. We infect the bladder with bacteria and allow it to grow on the catheter's surface. The bacteria buildup will eventually block the tube, preventing urine from reaching the bag.

These experiments are crucial because they require reproducibility and reliability. To ensure consistency, I make five-litre tanks of artificial urine each week. Real urine can be very variable depending on what someone has eaten or drunk. Mixing water with urea, and other salts like potassium and sodium chloride is what I do. It even smells just like the real deal.

Different drugs are judged on the time it takes for the catheter to stop working. They could be used to test the effectiveness of different drugs. The more time it takes to clear a catheter blockage, then the better the treatment. You will be amazed at the excitement and anticipation that comes with watching your urine slowly flow through a catheter encrusted with bacteria.

Of course I am not yet 12 months into my three-and-a-half-year project, and there is a long, long way to go before handing a patient a drug which will cure their infection. My research is helping to develop new antibiotic treatments for patients suffering from chronic UTIs that are not easily treated with current drugs.