The method allows researchers to focus on the moments when resistant and susceptible strains branch off from one another. This silences the background noise of random mutations that aren't associated with resistance.
"You're tuning out all the changes that happened to their common ancestors, which allows you to look specifically at what the differences between the daughter lineages were when resistance evolved," Farhat said.
The project used a large set of clinical strains collected from human populations rather than strains that were developed in the lab. They sampled strains from outbreaks in British Columbia, Rome, South Africa and Russia. The strains came from dozens of sites around the world, including most of the major lineages of susceptible TB currently circulating around the world. This large, diverse data set was crucial to gaining insight into how resistant strains evolve in human populations.
They also needed a community of clinicians and researchers who were prepared to work across disciplines
"Making progress on understanding and fighting complex, global diseases like TB requires a community of physicians and scientists who are not only each working in their own niches, but building a collaborative ecosystem to share data, perspectives and results in order to push the work forward," Murray said.
One key collaboration was with Eric Rubin, HSPH professor of immunology and infectious diseases, and Karen Keiser, a graduate research fellow at HSPH. One of the new sites of resistance was found in ponA1, a gene that is important to TB cell wall function. Rubin and Keiser introduced this mutation into laboratory TB strains and found a small yet significant elevation in their levels of resistance to the TB drug rifampi
|Contact: David Cameron|
Harvard Medical School