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Wisconsin chemists find a new chink in TB's armor

MADISON - The family of bacteria that causes tuberculosis (TB) and leprosy are notoriously sturdy. And although the diseases they cause have been held in check for the past 50 years by antibiotics, some strains are becoming increasingly resistant to existing therapy.

Now, however, a new chink has been found in the cellular armor that makes these infectious diseases difficult to treat. The discovery, reported today (May 9) in the online editions of the journal Nature Structural & Molecular Biology by a team of chemists and biochemists from the University of Wisconsin-Madison, opens the door to the development of a new family of antibiotics to treat diseases that still claim as many as 3 million lives annually worldwide.

"Most of the treatments we have for these diseases date from the 1950s," says Laura L. Kiessling, a UW-Madison professor of chemistry and the leader of the team reporting the new discovery. "Many traditional antibiotics don't work against tuberculosis."

The bacteria that cause tuberculosis are literally tough as nails. With unique multilayered cell walls, the microbes resist easy treatment.

Current drug regimens typically last up to six months and require a mix of as many as six different drugs. Because the drugs cause unpleasant side effects, and because patients often feel better after a month or two, many people do not complete treatments, a phenomenon contributing to a worldwide epidemic of multidrug-resistant TB. Adding to the problem, in less developed countries where TB is most common, health care is spotty and drug supplies are frequently inadequate.

Kiessling and her colleagues, working with the support of the National Science Foundation, have detailed the workings of a key enzyme that the bacterium requires to maintain the integrity of its cell walls. Enzymes are proteins that initiate chemical reactions within plant and animal cells.

"We've figured out how this enzyme works. If you knock it
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Contact: Laura L. Kiessling
kiessling@chem.wisc.edu
608-262-0541
University of Wisconsin-Madison
9-May-2004


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