New technique identifies M. tuberculosis genes

For most of this century, tuberculosis, or TB, has not been considered a major disease in the United States. In the late '80s, after a century of steady decline, the number of cases of TB in the United States began to increase due to increases in immigrants from countries where TB is prevalent, homeless people in crowded conditions, the elderly and AIDS patients. Although the increase in cases has been reversed in the last several years, more than 18,000 cases of TB were reported in the United States in 1998. Worldwide, TB remains a serious health problem. The World Health Organization has estimated that one-third of the world's population is infected with Mycobacterium tuberculosis, the bacterium that causes TB.

United States researchers have picked up their efforts over the past decade. One, Josephine Clark-Curtiss, Ph.D., research associate professor of biology at Washington University in St. Louis, and her colleagues have recently identified 15 M. tuberculosis genes that are expressed only when the bacteria are growing in the immune system's prime gatekeeper, a disease-fighting cell called a macrophage.

Using an elaborate new technique that is widely applicable to a host of different research situations, James Graham, Ph.D., a post-doctoral researcher in Clark-Curtiss' lab, captured DNA complementary to messenger RNA (called cDNA) of genes active in human macrophages, cells that engulf and degrade pathogenic bacteria, rendering them harmless.

But in the case of M. tuberculosis, the killer bacteria have found a way, once inside the macrophage, to prevent the development of a macrophage compartment known as the phagolysosome. This key compartment produces a number of enzymes that puts the coup de grace on M.tuberculosis.

Clark-Curtiss believes the 15 genes isolated in her laboratory play important roles in the pathogen's metabolism, propagation and self-protection once i

Contact: Tony Fitzpatrick
Washington University in St. Louis

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