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Plague agent helps UT Southwestern researchers find novel signaling system in cells

DALLAS The bacterium that causes bubonic plague would seem unlikely to help medical scientists, but researchers at UT Southwestern Medical Center have harnessed it to uncover a new regulatory mechanism that inhibits the immune system.

Three species of the Yersinia bacteria, known to cause plague and gastroenteritis, contain a small molecule, called a virulence factor, that the researchers have found modifies host enzymes critical to normal functioning.

"This type of modification has never been seen in cells and presents a new paradigm for how cells may regulate signaling," said Dr. Kim Orth, assistant professor of molecular biology and senior author of the study appearing in the May 26 edition of Science.

"Yersinia is a nasty pathogen that uses an arsenal of virulence factors to cause disease," she said.

When a cell is infected with a bacterial pathogen, it activates a chain of reactions involving enzymes. One enzyme adds a group of atoms containing phosphorus called a phosphate group to another enzyme, a process called phosphorylation, which spurs that enzyme to add a phosphate group to yet another enzyme, and so on. These "cascading" events trigger an appropriate immune response.

Yersinia, however, has the ability to prevent its host from mounting the response, enabling the bacteria to survive and multiply.

The researchers found that one of the Yersinia outer proteins, called YopJ, cripples these cascades by adding a small molecule called an acetyl group to two key sites on a host enzyme where the phosphate groups are usually added.

Because the host's enzymes are modified by acetyl groups, they can no longer be activated by phosphate groups, and the enzymatic cascade critical for triggering an innate immune response is not activated.

The internal signaling that YopJ affects is common to many species, from yeast to mammals. In addition, other pathogens that attack animals and plants use proteins th
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
25-May-2006


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