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New class of antibiotics stops pathogens in their genetic tracks

COLUMBUS, Ohio Researchers have found that a promising new class of antibacterial chemicals inhibits one of the most fundamental processes of life a cell's ability to express genetic material. Knowing exactly how these chemicals keep bacterial cells in check can help scientists make more effective antibiotics.

Like many bacterial inhibitors, this new class of compounds called the CBR703 series inhibits RNA polymerase, the key enzyme in gene expression. However, the unique mechanism that these compounds use to inhibit RNA polymerase was previously unknown and is first described in this week's journal Science.

"It's a long way between knowing that something will kill bacteria and figuring out the exact process by which the bacteria is killed," said Irina Artsimovitch, a study co-author and an assistant professor of microbiology at Ohio State University. "Other antibiotics also inhibit RNA polymerase, but the ones in this study use a radically different inhibitory mechanism."

According to the study, CBR703 inhibitors hindered the ability of RNA polymerase in Escherichia coli to perform crucial catalytic functions, such as building molecules of RNA. Compounds in the CBR703 series all are synthetic chemicals render RNA polymerase useless by binding to a specific place on the enzyme a necessary step in the process.

"Unless you know where the inhibitor binds, you can't draw any conclusions about how that inhibitor affects its target," Artsimovitch said. "On the other hand, once you have this information, you could predict if the inhibitor would be effective against a broad range of bacteria, as the binding site may not be the same in RNA polymerase enzymes from different bacteria."

She and her colleagues chose to study the effects of CBR703 inhibitors on E. coli, since the RNA polymerase enzyme in many pathogens is similar to that found in the E. coli bacteria. CBR703 compounds are not yet used as commercial antibiotics.


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Contact: Irina Artsimovitch
Artsimovitch.1@osu.edu
614-292-6777
Ohio State University
23-Oct-2003


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