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

1 year ago 121

In May, PhD students who are funded by the Medical Research Council (MRC) were invited to participate the Max Perutz subject penning grant 2021 and constitute a compelling portion astir their probe for the non-scientific reader.

From the galore entries received, the 10 that made the shortlist covered divers topics, including dementia, puerility adversity, the relation of genes successful schizophrenia and the usage of hypnosis to dainty psychosis.

The essays were judged by: the Observer’s Ian Tucker, the Science Museum’s subject director, Roger Highfield; Prof Fiona Watt, enforcement seat astatine the MRC, Andy Ridgway, elder lecturer successful subject connection astatine the University of the West of England successful Bristol, the writer and broadcaster Gaia Vince, and the researcher and intelligence wellness advocator Dr Furaha Asani.

At a virtual ceremonial past month, the £1,500 prize was presented to the winner, Vicky Bennett from the University of Bath, for her nonfiction astir her probe into repurposing drugs to dainty urinary tract infections.

Here we people the winning article, described by Roger Highfield arsenic “a gallant mode to marque unglamorous probe interesting.”

The winning essay

Vicky Bennett
Vicky Bennett, writer of the winning entry. Photograph: Courtesy of Vicky Bennett/Max Perutz prize

I’m a biomedical probe scientist. My laboratory essentials are a achromatic coat, bubbling liquid, and the occasional explosion. I marque groundbreaking discoveries each day. Crowds stitchery to marvel astatine my experiments and their life-saving implications.

This is astatine slightest my mum’s content of my PhD truthful far.

The world of my existent concern seems somewhat different. My shiny achromatic laboratory overgarment was astatine archetypal a fantastic summation to my wardrobe, but the galore tanks of infected urine connected my workbench are acold from glamorous. (In fact, shiny achromatic laboratory overgarment + infected urine = smelly yellowish laboratory coat). Instead of crowds of admirers, “the wee area” of our shared laboratory abstraction is actively avoided. The consequences of immoderate benignant of detonation are not worthy contemplating.

Welcome to the satellite of urinary tract corruption research.

Urinary tract infections (UTIs) are not peculiarly pleasant. They hap erstwhile bacteria from poo travel into interaction with and participate the outer opening of the urethra, the conduit that allows urine to travel from the bladder to the extracurricular of the body. If bacteria colonise the urethra, they past person nonstop entree to the bladder. This is the perfect situation for them to multiply and dispersed upwards to infect the kidneys, oregon adjacent participate the bloodstream.

For those fortunate capable not to person experienced a UTI, the predominant impulse to urinate and a achy stinging oregon burning sensation erstwhile passing urine are diagnostic symptoms. UTIs are communal for each ages, but evident anatomical differences mean that women are much predominant sufferers, arsenic a shorter urethra reduces the region bacteria indispensable question to scope the bladder. With up to 60% of big women suffering astatine slightest 1 UTI successful their beingness (compared to 12% of men), galore spot them arsenic an awkward but inevitable portion of life. Data connected transgender acquisition of UTIs is limited, but proposal sites study they tin beryllium an contented for genital tuckers and trans men taking testosterone. Sufferers person adjacent gone truthful acold arsenic to picture their experiences successful opus form. See Love opus for my UTI by YouTuber Lex Croucher for 1 of my favourite examples.

A abbreviated people of antibiotics volition wide astir infections. But the fig of bacteria resistant to antibiotics is increasing. Someone with an corruption which was erstwhile curable successful a fewer days whitethorn present effort respective antithetic antibiotics earlier uncovering 1 that works. And adjacent if your symptoms bash wide up, it whitethorn beryllium that the bacteria person not been afloat eradicated, with astir 30% of infections returning wrong six months. Many radical indispensable judge a beingness of chronic recurring UTIs and near-permanent symptoms.

Every UTI besides has the hazard of processing into a life-threatening kidney oregon bloodstream infection. This hazard increases with age, and for those with underlying wellness conditions. The ever-growing menace of antibiotic absorption means that chronic and terrible infections are becoming much common. Even that good known mythical cure that is cranberry foodstuff volition not person immoderate effect against multidrug-resistant bacteria.

So, the solution is to find immoderate new, amended antibiotics, right? Something that kills bacteria rapidly and is hard for bacteria to go resistant to. This fundamentally is the purpose of my PhD project. I americium trying to place circumstantial parts of bacteria that would marque bully targets for caller antibiotics to attack. I volition past usage a machine modelling strategy to place existing drugs which could beryllium utilized successful a caller mode to deed these targets and termination the bacteria. These travel from immense databases of millions of drugs utilized for immoderate intent successful medicine, not needfully existing antibiotics. This is simply a process called cause repurposing. If palmy it volition trim the clip and outgo associated with caller antibiotic development.

This leads america backmost to my urine tanks. In my probe radical we enactment with a bacteria called Proteus mirabilis, a communal origin of catheter-associated urinary tract infections (CAUTIs). Urinary catheters are the astir commonly utilized aesculapian devices. The catheter is simply a agelong flexible conduit inserted done the urethra into the bottommost of the bladder and is connected to a urine postulation container extracurricular the body. They are utilized successful radical of each genders with aesculapian conditions that marque it hard for the bladder to bare naturally, arsenic good arsenic earlier oregon aft immoderate types of surgery. Depending connected the situation, the catheter could beryllium impermanent oregon permanent.

But the beingness of a catheter makes it easier for UTIs to develop. Bacteria turn overmuch much easy connected the catheter surface, and the conduit provides a nonstop pathway for them to participate the urethra and the bladder. As the bacteria physique up, they volition yet artifact the conduit and forestall urine leaving the bladder. This causes urine to cod successful the bladder, wherever it tin travel backwards towards the kidneys, expanding the likelihood of life-threatening kidney and bloodstream infections, arsenic good arsenic causing a immense magnitude of symptom from the urinary retention itself.

We recreate this concern successful the laboratory by utilizing catheters inserted into replica solid bladders. A pump strategy pushes urine done the bladder and into the catheter astatine assemblage somesthesia truthful we tin show the effects of our experiments successful arsenic realistic a mode arsenic possible. We infect the solid bladder and permission the bacteria to turn connected the catheter surface, wherever the buildup of bacteria volition yet artifact the conduit and halt urine from entering the postulation bag.

A cardinal facet of these experiments is reproducibility and reliability of results. Real urine is precise adaptable depending connected what idiosyncratic has been eating oregon drinking, truthful I walk a time each week making up five-litre tanks of artificial urine to usage successful my experiments to guarantee consistency. This involves mixing h2o with urea and assorted salts specified arsenic potassium and sodium chloride. It adjacent smells similar the existent thing.

The clip taken for the catheter to artifact determines the occurrence of antithetic drugs. These could beryllium tested successful respective ways: either by being flushed into the bladder done the catheter, dissolved successful the urine, oregon applied arsenic a coating to the catheter earlier it is inserted. The longer the clip to catheter blockage, the much promising the treatment. And you would not judge the anticipation and excitement caused by watching urine dilatory drip done a bacteria-encrusted catheter.

Of people I americium not yet 12 months into my three-and-a-half-year project, and determination is simply a long, agelong mode to spell earlier handing a diligent a cause which volition cure their infection. However, I truly anticipation that my probe volition enactment the improvement of caller antibiotic treatments to assistance patients with CAUTIs, chronic UTIs not treatable with existing drugs, and anyone who is fed up with that burning sensation erstwhile they pee.