Next-Generation Treatment for UTIs May Focus on Fitness Genes

Urinary tract infections (UTIs) can occur with no apparent cause, and as effectiveness of antibiotics fades, treating them is also becoming less predictable. University of Michigan Medical School researchers have identified bacterial genes that help the infections spread, providing a potential new target for treating UTIs, a global public health concern mostly affecting women. UTIs lead to lost work time, emergency room visits and healthcare spending of $3.5 billion in the United States.

The research findings, published in this week's Proceedings of the National Academy of Sciences, reveal the specific genes expressed by Escherichia coli, the bacteria that most often causes UTIs in otherwise healthy people.

"The bacterium is becoming resistant to currently available antibiotics, making it imperative to develop new treatment and prevention strategies," says senior study author Harry T. Mobley, PhD, the Frederick G. Novy professor and chair of the Department of Microbiology and Immunology at the University of Michigan Health System. "The next logical step is to identify and develop therapies that selectively block these UTI-specific genes."

In the study of 42 women, 7.7 percent had infections that were resistant to ciprofloxacin and 15.3 percent did not respond to trimethoprim/ sulfamethoxazole, two antibiotics commonly used for treatment.

The U-M team used genomic screening tools to take a deeper look at the mechanisms for infection. Rather than the expected virulence factor, the newly discovered E. coli-specific genes helped protect the bacterial species from the toxic effect of metal ions the body uses to fight infection.

Attacking this function, and other mechanisms that promote survival of the bacteria in the urinary tract, may be a strategy for new microbial agents, authors say.

The U-M has a remarkable record in research of molecular mechanisms leading to bacterial infections. The Mobley research team is among scientists identifying a potential approach for a vaccine to prevent urinary tract infections.

Additional authors are Sargurunathan Subashchandrabose, Tracy H. Hazen, Ariel R. Brumbaugh, Stephanie D. Himpsi, Sara N. Smith, Robert Ernst and David A. Rasko.

Research was supported in part by the National Institute of Diabetes and Digestive and Kidney Disease of the National Institutes of Health under award number DK09477. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by a Research Scholars Fellowship from the American Urological Association-North Central Section, administered by the Urology Care Foundation, and funds from the State of Maryland.

Reference: Host-specific induction of Escherichia coli fitness genes during human urinary tract infection. PNAS, published ahead of print Dec. 8, 2014, doi:10.1073/pnas.1415959112