Synchrotron research examines novel antibiotic approach to E Coli UTIs

What began as a conversation between two animal lovers on a long horse ride turned into a successful research collaboration between the Canadian Light Source (CLS) and the University of Saskatchewan (U of S) that will provide valuable research for treating difficult urinary tract infections (UTI).

Veterinarian Dr. Patricia Dowling and CLS Industrial scientist Julie Thompson met each other while endurance riding near Saskatoon. With their horses keeping the pace, the two began discussing a potential research project that could help both people and animals.  Once they had U of S PhD student Katherine Ball onboard, the project began to take shape.

Their study would look at UTIs in humans and animals to understand why that E. coli bacteria are increasingly resistant to standard antibiotic treatments, leading researchers to fear we are rapidly running out of treatment options.

“Bacteria do whatever they need to do to survive in a hostile environment,” said Dowling. “We were hoping to find a novel way to combat E. coli infections in the urinary tract, which affect humans, dogs, and cats in similar ways.”

Dowling, a professor of veterinary clinical pharmacology at the Western College of Veterinary Medicine (WCVM) specializes in the identification and treatment of diseases, and she says that because UTIs are a huge issue in both humans and animals, animal models can be very useful in evaluating potential treatments for people.

Dowling, Thompson, Ball and their colleagues, investigated a novel way of treating UTIs caused by E. coli using a mouse model, and recently published their results in the Antimicrobial Agents Chemotherapy journal.  UTIs are among the most common bacterial diseases in people. Over half of all women, and approximately 10 per cent of men, experience at least one bout of cystitis, the most common type of UTI, by their mid-thirties. UTIs are also the most common type of hospital-acquired infection in Canada.

E. coli infections are extremely tricky to deal with though, says Dowling, as they can hide inside the cells that line the bladder, craftily hiding from the antibiotics we using to try to kill them

“We were looking far outside the box of traditional antibiotics,” said Dowling. “So we looked at different metals with antimicrobial properties. Gallium had been used as a drug orally, and since UTIs are usually treated with oral drugs, gallium seemed like a good thing to test.”

The team tested the success of the gallium on the E. coli samples taken from the kidney, liver, and bladder of mice to identify where the E.coli bacteria were located in the body and how the gallium and other metals reacted.

“The most fascinating part of the experiment was imaging where the gallium went within the bladder,” said Thompson, industrial staff scientist at the CLS. “We could see how it was reacting. We could locate where the drug was going.”

“We did achieve big results,” said Dowling. “The gallium went where we wanted it to, but unfortunately the concentrations achieved were not sufficient for treatment of E. coli infections. Although, it might be suitable for treatment of other bacterial pathogens.”

The researchers believe using the synchrotron to locate the drug in tissues will ultimately determine which forms of the drug can be used, and will open up a whole new area of research into treating UTIs and other infections.

Acknowledgments: Katherine R. Ball, Francesca Sampieri, Manuel Chirino, Don L. Hamilton and Patricia M. Dowling from the University of Saskatchewan; Robert I.R. Blyth and Julie Thompson from the Canadian Light Source synchrotron; T.K. Sham, University of Western Ontario. This research was funded by the Collaborative Health Research Projects (CHRP), a joint initiative between the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR).