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Bad news for pathogenic bacteria: Scientists find protein essential for bacterial survival

COLUMBUS, Ohio Further investigation into how the common organism Escherichia coli regulates gene expression has given scientists new ideas for designing antibiotics that might drastically reduce a bacterium's ability to resist drugs.

The findings, reported in the current issue of the journal Cell, suggest that bacteria rely on a key protein in order to properly regulate gene expression a process fundamental to cell survival.

This protein, called DksA, coordinates the expression of numerous genes in response to environmental signals.

Figuring out how to block DksA production in harmful bacteria may help scientists develop antibiotics that these bacteria are less likely to resist, said Irina Artsimovitch, a study co-author and an assistant professor of microbiology at Ohio State University.

The current study suggests that DksA is the glue that holds together two key components of bacterial gene expression a molecule called ppGpp and an enzyme called RNA polymerase. RNA polymerase carries out transcription, the first step in gene expression.

In recent work, Artsimovitch and her colleagues discovered that ppGpp regulates gene expression by controlling amino acid production in bacteria. A cell makes ppGpp when amino acid levels are low, and ppGpp tells a cell to go dormant until amino acid levels return to normal.

"But there was something missing from the ppGpp story," Artsimovitch said. "We knew that ppGpp had a dramatic effect on gene expression, but for some reason that effect was drastically decreased when we conducted experiments in the laboratory."

Work by other researchers had suggested a link between DksA and the ppGpp-initiated stress response in the cell. But scientists couldn't agree on what role, if any, DksA played in the effect of ppGpp on gene expression.

Working with a team of researchers led by Dmitry Vassylyev, a scientist with the RIKEN
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Contact: Irina Artsimovitch
artsimovitch.1@osu.edu
614-292-6777
Ohio State University
5-Aug-2004


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