Tuberculosis gene may explain dormancy.

The tuberculosis bacterium is nothing if not an artful dodger. Over the years, it has proved itself capable of eluding almost every trap mankind has laid.

Now, researchers have gained an important insight into an ancient conundrum-how the tuberculosis microbe manages to remain dormant in the lungs for years before flaring up into active disease. Not surprisingly, the secret appears to be genetic. Tuberculosis contains a gene called SigF, which regulates dormancy, report William R. Bishai of Johns Hopkins School of Hygiene and Public Health in Baltimore and his coworkers.

When the bacterium is under stress, as it is in the hostile environment of the lungs, SigF may enable it to sporulate, or turn itself into a seed, in order to protect itself, says Bishai. This gene resembles sporulation genes identified in other bacteria.

Doctors had discarded sporulation as a possible explanation for tuberculosis' remarkable staying power because no one has ever successfully coaxed the bacterium to form spores in the lab. But that doesn't mean it can't happen in the body, say Bishai and his coworkers in the April 2 Proceedings of the National Academy of Sciences.

'In all honesty, we were hoping to find something like this,' Bishai says. 'We didn't expect to find a sporulation gene first off. That was exciting.'

The presence of the gene is not proof of its activity, however, says Bishai, adding that no one has retrieved latent microbes from an infected individual.

The key step involves destroying the SigF gene-a challenge in itself-to see whether this affects the bacterium's ability to become dormant.

If the gene functions as Bishai and his coworkers hypothesize, the finding could hold important implications for treatment. 'Suppose we could develop drugs that affect the shift to dormancy?' Bishai asks. If scientists could manipulate the bacterium's life cycle, 'we could treat infections for shorter periods.

We could [treat] multidrug-resistant TB simply by putting the [microbes] into a dormant state.'

Researchers might also be able to develop a vaccine strain simply by knocking out the SigF gene, Bishai says. Without the gene, the bacterium theoretically would lose its ability to protect itself against the immune system-unless, of course, the artful dodger has a new trick up its sleeve.