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Genes That Let TB Linger

Even when it's not deadly, tuberculosis is persistent, and that makes the respiratory disease difficult to wipe out. Now, two groups of researchers have identified genes that may help TB resist the immune system. If so, the proteins made by these genes could be good targets for new drugs.

The tuberculosis bacterium has been called the world's most effective pathogen. It lurks in one-third of the world's population and kills an estimated 2 million people each year. In most, the infection remains latent, but in some it explodes in disease years to decades later. New drugs are sorely needed because more and more TB bacteria are becoming resistant to current medications.

To figure out TB's devious tricks, a team led by Stanford University microbiologist Stanley Falkow investigated a close relative of TB, one that infects frogs rather than mammals. They tagged a dozen genes that turn on when the bacteria grow inside clusters of immune cells in the frog, the same spot where TB hides in humans. When they knocked two of these genes out of the bacterium's genome, it couldn't survive in a lab culture of immune cells, they report in the 26 May issue of Science.

The second team, led by microbiologist William Jacobs of Albert Einstein College of Medicine in New York City, worked with another cousin of TB called bacillus Calmette-Guérin (BCG). They identified a gene that allows the microbes to join up in culture like long cords--a characteristic that is typical of especially virulent pathogens. Mutations that stopped this cord formation also prevented BCG from killing infected mice, they report in the April Molecular Cell.

The new research is "clever and exciting," says infectious disease specialist William Bishai of Johns Hopkins School of Public Health in Baltimore. "If we understand how the organism adapts and persists, we'll be much better off in terms of drug development."