Finding May Lead to New Drugs for Urinary Infections

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Finding May Lead to New Drugs for Urinary Infections
Researchers seek way to destroy bad, not good, E. coli

February 20, 2009
By Robert Preidt
HealthDay

FRIDAY, Feb. 20 (HealthDay News) -- Potential targets for new drugs to fight the bacteria that cause many urinary tract infections have been identified by U.S. researchers.

Two molecules called yersiniabactin and salmochelin enable E. coli to steal iron from their hosts, which makes it easier for the bacteria to survive and reproduce. Identifying the two molecules -- called siderophores -- could help lead to the development of antibiotics that target pathogenic E. coli strains without harming beneficial bacteria in the gut.

The findings appear in the Feb. 20 issue of PLoS Pathogens.

"When we treat an infection with antibiotics, it's like dropping a bomb -- nearly everything gets wiped out, regardless of whether it's helpful or harmful. We'd like to find ways to target the bad bacteria and leave the good bacteria alone, and these siderophores are a great lead in that direction," study author Jeff Henderson, of the Center for Women's Infectious Disease Research at Washington University School of Medicine in St. Louis, said in a Public Library of Science news release.

The E. coli bacteria that cause urinary tract infections might come from the human gut, where several strains of the bacteria reside. But it's believed that other strains help aid digestion and block other infectious organisms.

For their study, Henderson and his colleagues used a method called metabolomics to study the differences between disease-causing and friendly E. coli strains. Metabolomics involves analyzing all the chemicals produced by a cell, including growth signals, toxins and waste products.

"This allows us to look at the end products of many genes working together," senior study author Scott Hultgren explained in the news release. "We assess what all the various assembly lines are producing and which products disease-causing bacteria prefer to make, such as certain siderophores."

Drugs that block or disrupt the activity of the proteins that make siderophores could be one way to fight disease-causing bacteria. Another approach is what the researchers call a "Trojan horse" strategy.

"To steal iron, siderophores have to be sent out from the cell, bind to the iron and then be taken back into the cell," Henderson said. "If we can design an antibiotic that looks like a siderophore, we might be able to trick only disease-causing bacteria into taking up the drug while leaving other bacteria alone."

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