April 21, 2021

I, Science

The science magazine of Imperial College

Reports of the resistance of UTIs to antibiotics are on the rise. Can a new method focused on preventing the bacteria from clinging to the lining of the urinary tract help?

Serious concerns were raised earlier this year, when an american woman reportedly became the first patient to have a urinary tract infection (UTI) resistant to all antibiotics. This even included colisin – an especially strong drug reserved for ‘nightmare bacteria’. Combined antibiotic therapies had until now been effective in killing the evermore resistant strains of the bacteria causing UTIs. However, new research has just been published in the Journal of Medicinal Chemistry, announcing a new class of drugs which could potentially prevent the bacteria from developing resistance.

UTIs are very common infections, prevalent mostly amongst women, and tend to occur when bacteria from the gut enter the urinary tract through the urethra. The pathogens then colonize the bladder tissue, by binding to its walls. While most cases can be treated with short courses of antibiotics, since the 1970s multidrug resistant pathogens have become a serious threat – 20-40% of cases now recur within 6 months of the initial diagnosis.

The timely new research, instead of trying to kill the bacteria, focused on developing small molecules that prevent the bacteria from clinging to the linings of the urinary tract. This new class of molecules inhibits the function of FimH, a critical component produced by bacteria to enable adhesion to other cells, for example in the urinary tract lining.

Other research teams had managed to produce similar compounds, called O-mannosides. However, these proved to break down too quickly during animal testing. James W. Janetka and his team, based in the U.S., replaced molecular bonds in O-mannosides with carbon-based linkers, creating more stable versions called C-mannosides. Testing in mouse models of acute and chronic UTI, has so far shown the compounds to be stable. Ongoing preclinical studies will identify which C-mannoside will move into clinical trials. This is definitely  good news, as the solution is urgent.

According to the NHS, up to 20% of women will suffer this painful condition at some point in their lives. Men may also experience these, and although less often, the cases tend to be more serious. Most cases, known as lower UTIs, affect the bladder (cystitis) or urethra (tube that carries urine out of the body). If untreated, the bacteria may travel up the urinary tract and colonize the ureters (the duct by which urine passes from the kidney to the bladder) and the kidneys, with dangerous potential of spreading through the bloodstream. It sounds painful just imagining it, so it is comforting knowing a potentially effective treatment is on its way!

It may be a while before the drug is commercially available, but this research could pave the way for the development of other antibiotic-sparing drugs, which are desperately needed for other infectious diseases.

Marcela Leite is studying for an MSc in Science Communication.

Banner Image: UTI word cloud, ibreakstock