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Researchers identify the pattern of gene-expression changes for tuberculosis in a living host

DALLAS March 22, 2004 Researchers at the Center for Biomedical Inventions at UT Southwestern Medical Center at Dallas have identified the genetic changes that Mycobacterium tuberculosis, the bacterium that causes tuberculosis, undergoes during infection of a living host.

For the first time, researchers have adapted gene-chip technology to carry out genomic analysis of gene expression during the course of infection not only for M. tuberculosis, but for any pathogen. The findings will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and are currently available online.

To analyze multiple questions about the pathogenesis of tuberculosis, the researchers used gene chips, which allowed them to assess the pattern in which bacterial genes are expressed during the course of infection. This work demanded two years of technology development to establish a protocol that allowed high-throughput analysis of genes that were expressed in a pathogen that was extracted from an infected animal, rather than simply grown in culture.

"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 Dr. Stephen Albert Johnston, director of the CBI and one of the senior authors of the study. "We see it as a tool for vaccine and drug development against disease and the threat of biological weapons."

In the PNAS paper, researchers discuss how the tuberculosis bacterium had previously undergone genetic analysis based only on lab tests outside of a living organism. Once the entire genome of M. tuberculosis was sequenced, Drs. Johnston and Adel Talaat, then a postdoctoral researcher at UT Southwestern, began using high-speed microarray techniques, or gene-chip technology, to analyze the bacterium's gene expression at different stages of infection in mice.

Since other pathogens have
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Contact: Steve OBrien
Stephen.obrien@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
22-Mar-2004


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