A molecular chink in the armor of tuberculosis

November 4, 1999—One of the world's deadliest microbes, Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), has inadvertently tipped off researchers to a potential chink in its armor. Researchers from the Howard Hughes Medical Institute (HHMI) have identified a lipid molecule that must be produced by M. tuberculosis if the bacterium is to infect the lungs of mice.

"The unique lipids of M. tuberculosis likely play key roles in making the bacterium the world's most successful pathogen—having infected more than one in three people on the planet," said William Jacobs, an HHMI investigator at Albert Einstein College of Medicine. "This work is the first to establish definitively that exported lipids are required for the bacteria to grow in the lungs."

"What really distinguishes tuberculosis as a pathogen is that it passes from person to person by aerosol infection, but it first has to invade the lungs to propagate," said Jacobs. "If we understood how TB propagates in the lungs, we’d have a much better idea of how to combat the infection."

The rapid emergence of drug-resistant strains of M. tuberculosis has placed a premium on the need to develop new ways to stop TB infection. One route, pursued by Jacobs and his colleagues, is to understand at the molecular level how M. tuberculosis invades the lungs and thrives in this otherwise hostile environment. In time, observations from such studies could pave the way for improved vaccines and drugs to prevent TB, which kills more people each year than AIDS or malaria.

In studies published in the November 4, 1999, issue of the journal Nature, Jacobs and colleagues Jeffery Cox and Bing Chen of Albert Einstein College of Medicine and Michael McNeil of Colorado State University inserted bits of gene-disrupting DNA called transposons at random locations i

Contact: Jim Keeley
Howard Hughes Medical Institute

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