May 2004

National Science Foundation

Researchers open new line of attack on tuberculosis

Findings could show how to breach the bacterium's tough cell wall

ARLINGTON, Va.-Chemists and biochemists at the University of Wisconsin-Madison, supported in part by the National Science Foundation (NSF), have discovered a new chink in the armor of the bacterial family that causes diseases such as tuberculosis and leprosy.

The researchers' findings, which are reported today (May 9) in the online edition of the journal Nature Structural & Molecular Biology, could lead to the development of a new family of antibiotics to treat those afflictions, which claim up to 3 million lives around the world every year. This prospect is especially welcome given the rapid spread of tuberculosis strains that are resistant to existing drugs.

Microbes that cause tuberculosis and leprosy, and related bacteria, are particularly tough adversaries because of their unique, multilayered cell walls, which render them virtually invulnerable to easy treatment. In the research reported today, however, UW chemist Laura L. Kiessling and her team have detailed the workings of a key enzyme the bacteria use to maintain the integrity of their cell walls. Enzymes are proteins that initiate chemical reactions within bacteria, plant and animal cells.

"We've figured out how this enzyme works," says Kiessling. "If you knock it out, the bacteria aren't viable."

Kiessling cautions that it takes years and many millions of dollars to develop a new drug. Nonetheless, this discovery opens up a whole new line of attack against TB and leprosy. "Because we understand the mechanism better, we can design inhibitors specific to this enzyme."

In the paper, Kiessling acknowledges support from an NSF Young Investigator award. "It is gratifying to see that seminal funding from NSF has helped Dr. Kiessling develop into a leading organic chemist," says NSF program officer, George Rubottom. "Her research, which covers the spectrum from synthesis to enzyme mechanism, highlights the unique role chemistry can play in solving extremely important biological problems."



A more detailed press release about this work will be available after the embargo lifts on the University of Wisconsin-Madison web site: http://www.news.wisc.edu/.

NSF Media Contact: M. Mitchell Waldrop, (703) 292-7752, [email protected]

UW-Madison Media Contact: Terry Devitt, (608) 262-8282, [email protected]

NSF Program Officer: George Rubottom, (703) 292-4965, [email protected]

Principal Investigator: Laura L. Kiessling, (608) 262-0541, [email protected]

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