Gene Activation in Tuberculosis Counters Host Immune Response

Researchers have adapted high-speed gene chip microarray technology to study the pattern of gene activation in Mycobacterium tuberculosis cells growing in normal mice, immune-deficient mice, and in culture.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) spent more than two years developing a protocol that allowed high-throughput analysis of genes that were expressed in a pathogent extracted from an infected animal, rather than simply grown in culture.

Using this tool they found that M tuberculosis cells removed from mice 21 days after infection showed activity in a set of 67 genes that did not function in cells grown in immune-deficient mice or in culture. The activity of these genes was thought to be required for avoidance of the host's immune response. The finding that bacteria from immune deficient mice displayed the same lack of gene activity as those from culture calls into question the use of immune-deficient mice for drug development studies. These results were published in the March 18, 2004, online issue of the Proceedings of the [U.S.] National Academy of Sciences.

"This is an example of how the high-throughput system is a new avenue to study a variety of pathogens and how they affect living hosts,” said senior author Dr. Stephen Albert Johnston, director of the Center for Biological Inventions at the University of Texas Southwestern Medical Center. "We see it as a tool for vaccine and drug development against disease and the threat of biological weapons. By identifying the genes that cause disease progression in vivo, we can begin to piece together the knowledge that will allow us to discover better targets for drug therapies.”




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