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Scientists Identify Molecular Target For Tuberculosis Drug Treatment

In a study with major implications for improving tuberculosis (TB) treatment, researchers have identified the exact part of the disease-causing microbe that is targeted by isoniazid, the most widely used TB medication.

Tuberculosis now infects some 1.9 billion people worldwide, one-third of the world's population. The World Health Organization projects that in the next decade, 300 million more people will become infected, 90 million will develop tuberculosis and 30 million will die from it. As the number of new cases increases, multi-drug-resistant strains of Mycobacterium tuberculosis have made treatment more and more difficult.

"Tuberculosis cannot be fully controlled with existing medications," says NIAID Director Anthony S. Fauci, M.D. "We desperately need new drugs to combat this worldwide public health problem."

The new findings will allow scientists to understand and predict how certain strains of M. tuberculosis become drug-resistant. The research also has generated a way to screen potential anti-TB drugs very fast, accelerating the pace of drug development.

"With tests based on these findings, we'll be able to screen thousands of anti-TB compounds in an assay that takes only a few minutes, instead of the three weeks required for normal tests," says Clifton E. Barry III, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID). "I think we have the perfect new tool for developing new drugs against TB."

The research was a collaborative project of Dr. Barry's team and NIAID grantee James M. Musser, M.D., Ph.D., and colleagues at the Baylor College of Medicine in Houston, Texas. Their report appears in the June 5, 1998, issue of Science.

Although isoniazid has been widely used to treat people with tuberculosis, until now no one knew exactly how it worked, and why it no longer works on certain TB strains. Dr. Barry and his colleagues discovered that the drug attacks a protein, called KasA, that the bacterium nee
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Contact: June Wyman
jwyman@nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
4-Jun-1998


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