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Research Trying To Fool Bacterium

Michael C. Purdy/WASHINGTON UNIVERSITY SCHOOL OF MEDICINE

Differences in the way they use their genes cause different strains of the E. coli bacterium to take on different hues. The flask in the foreground contains a strain of bacteria that makes compounds linked to urinary tract infections, while the flask in the background contains a strain that does not make those compounds. Scientists are hoping to develop drugs that specifically target infection-causing strains of bacteria like those in the foreground beaker.

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Published: March 3, 2009

Updated:

The bacterium that causes infections of the urinary possess the molecular tools to steal what it needs from its hosts. Researchers, however, are attempting to turn the tables and use those tools to kill E. coli.

Researchers at the Washington University School of Medicine, in St. Louis, and the University of Washington have been studying molecular compounds known as siderophores. Siderophores help E. coli take the iron molecules they need to survive and reproduce.

They are trying to exploit siderophores to kill the strains of E. coli that can cause urinary tract infections, or UTIs, without harming bacteria that perform beneficial roles.

"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," says Dr. Jeff Henderson, a Washington University infectious disease specialist who treats patients with UTIs. "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."

Henderson was the lead author of a research report on siderophores that was published online Feb. 12 by the journal by PLoS Pathogens.

Henderson and his colleagues have been using a technique called metabolomics to study the differences in E. coli strains. Unlike studying the genes of cells, metabolomics looks at all the chemicals they produce.

"We assess what all the various assembly lines are producing and which products disease-causing bacteria prefer to make, such as certain siderophores," said one of Henderson's colleague Scott Hultgren, a professor of molecular microbiology.

The researchers found that E. coli found in the urinary tract produce more yersiniabactin and salmochelin, two siderophores that help bacteria scavenge iron, than E. coli from the gut.

One way to keep E. coli from causing UTIs could be to find a way to disrupt the proteins that have a role in producing siderophores, the researchers say. Another way, however, could be devising a "Trojan horse" strategy.

"If we can design an antibiotic that looks like a siderophore," Hultgren said, "we might be able to trick only disease-causing bacteria into taking up the drug while leaving other bacteria alone."

Funding from the Burroughs Wellcome Fund and the National Institutes of Health supported this research.

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