They discovered that a specific set of tuberculosis genes was activated only in healthy mice 21 days after the initial infection, a critical time in the progression of the disease in humans and other animals. This indicates that these genes are activated to help the pathogen survive within the host.

"We found that some genes are turned down so they stay below the immune system's radar," said Dr. Johnston, professor of microbiology. "The bug (tuberculosis) acts in a stealthy way, hoping not to become a target of the host's immune system but needing to stay just active enough to continue surviving."

Some genes were expressed only if the pathogen was active in an animal model. Infection in lab cultures - previously the only way that tuberculosis has been studied at the genetic level - did not express the same genetic responses in the tuberculosis pathogen. The new findings indicate that infectious diseases need to be studied in live animals models if meaningful results are to be attained.

"Understanding bacterial gene expression in vivo is central to our understanding of how bacteria colonize, invade and interact with or disrupt the normal host-cell functions and eventually produce disease," the researchers write.

The study was funded by the National Institutes of Health and Defense Advanced Research Projects Agency. This work was carried out in collaboration with the Animal Model Development Center at the University of New Mexico Health Science Center.