Grant: Collaborative Health Research Projects

Urinary tract infections are among the most common bacterial diseases of humans and animals. Most of these infections are caused by uropathogenic strains of the bacteria Escherichia coli. Over half of all women and approximately 10% of men experience at least one bladder infection, the most common type of urinary tract infection. The treatment of urinary tract infections caused by uropathogenic E. coli is complicated because these bacteria spend part of their life cycle within the epithelial cells that line the bladder, protected from the immune system and from many antibiotics. Because only a few of the currently available antibiotics penetrate bladder epithelial cells, the increasing occurrence of antibiotic resistant uropathogenic E. coli infections leaves few, and in some patients, no appropriate drug choices for treatment. Treatment failure can result in infertility, kidney infection, bloodstream infection, and death. The failure of traditional antibiotic therapy to cure resistant uropathogenic E. coli infections prompted us to explore novel alternatives, such as the metal gallium. Gallium is known to accumulate at sites of infection in the body, and has strong antibiotic activity. We aim to determine if gallium compounds arrive at, and eradicate the bacteria living in bladder epithelial cells during a urinary tract infection. Using conventional laboratory techniques, it is very difficult to accurately determine the chemistry and location of drugs within cells. However, the intense, highly focused x-rays generated at the Canadian Light Source synchrotron can be used with a powerful microscope to analyze the chemistry of tissue samples. Using this method, we will be able to visualize gallium distribution in bladder epithelial cells in mice, and we will be able to determine if the gallium actually enters the bacteria that are hidden in the bladder cells. This will provide valuable insight into how gallium compounds can be used to provide an effective alternative to traditional antibiotics for treating infections that affect millions of Canadians.