Urinary tract infections (UTIs), which are primarily caused by uropathogenic Escherichia coli (UPEC), are becoming more difficult to treat as antibiotic resistance rises. Around one in 40 women suffer from recurrent UTIs. Vaccines are not currently available for use in the United States.
A new report by University of Michigan Medical School researchers in the Proceedings of the National Academy of Sciences has identified a new strategy for UTI prevention using a molecule required by the pathogenic E coli.
The pathogenic bacteria that cause UTIs use an iron-scavenging molecule, or siderophore, to take advantage of the iron supply used by host cells. That aids the bacteria in taking hold and replicating inside the bladder, and promotes virulence. The siderophores are unique to the immune system of the host and can evade it. That has made them attractive targets for vaccines. In a new development in the use of siderophores in UTI prevention, scientists tried applying two different ones to the inside of the noses of mice a few times over a period of two weeks.
The individual application of the siderophores only provided a modest amount of protection against UTIs – in the experiments, the mice modeled UTIs after receiving a direct application of UPEC to their bladders. The researchers tried applying the siderophores at the same time, also utilizing a carrier protein. Using that strategy in the mice, an immune response was observed that provided some protection against UTIs.
"We saw efficacy more in the kidney than in the bladder, suggesting that this approach may be most useful in preventing advanced UTIs," said first author and research fellow Laura Mike. "Our next challenge is creating a combination vaccine that also employs proteins that UPEC bacteria use to bind their iron-laden siderophores, and test other adjuvants to increase the response."
This work is the best use of siderophores in the prevention of UTIs. Previous research has attempted to use a vaccine made up of proteins from the UPEC. Using the vaccine with the siderophore could be a way to totally prevent UTIs. Recent research, outlined in the video below, has shown that cranberry juice is not an effective way to prevent UTIs, making the work more urgent.
Since other pathogenic bacterium also produce siderophores, this approach might be useful in the fight against other bugs. "Using proteins that are found on the surface of bacterial cells as the basis for vaccination may lack efficacy because of the variability of the exact protein structure," said Harry Mobley, Ph.D., senior author of the new paper and chair of the Department of Microbiology and Immunology at UM. "But siderophores are the same across most gram negative enteric bacteria that cause some of the worst infections. This is a step along the journey, but it's an encouraging one."
Source:
AAAS/Eurekalert! via
University of Michigan Health System,
Scientific Reports,
PNAS
