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Researchers untangle genetics of drug resistant TB
Date:9/1/2013

f the cell walls might confer resistance to a wide variety of drugs," said first author Maha Farhat, HMS instructor in medicine and assistant physician at Massachusetts General Hospital.

"Until now, people assumed that single mutations conferred high-level resistancea strain either had them or did notbut our results challenge that paradigm," Murray said. "Knowing that small changes early in the evolution of resistance open the door for big changes, or that a single change is a gateway to global resistance, would be important clues in our struggle to outrace evolving drug resistance."

Murray is part of a network of researchers and physicians working to develop a holistic, integrative approach to understanding and treating TB. In addition to her role as a researcher at HMS, she is also an associate professor of medicine at Brigham and Women's Hospital and professor in the Department of Epidemiology in the Harvard School of Public Health (HSPH), director of research at Partners in Health and director of the HMS Global Health and Social Medicine Research Core.

"We're not only implementing programs and documenting outcomes, we're using our access to clinics around the world to further basic scientific research, which will ultimately help improve standards of care," Murray said.

To find the novel drug-resistance genes, Farhat, Murray and collaborators adapted tools from evolutionary biology known as "phylogenetics." Phylogenetics allows the study of relationships within populations of organisms. It was originally developed to trace the path of evolution and to calculate how once-related organisms diverged onto different branches of the tree of life over many tens of thousands of years.

The team adapted these tools to measure the rapid-fire evolution of drug-resistant TB in the clinic.

They examined the whole genomes of 116 newly sequenced and 7 previously sequenced strains of TB. The sample included 47 strains with
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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