39 new genes linked to the TB's elevated drug resistance were identified using a new method of analyzing whole genome sequences.
The new data suggests that acquiring resistance is a multistep process, perhaps requiring low-level resistance mutations prior to the ones that are well known.
The findings also suggest that some of these new genes are involved in resistance that may confer 'global' resistance traits, helping strains become resistant to a group of antibiotics rather than just one or a single class.
To find the novel drug-resistance genes, Maha Farhat, HMS instructor in medicine and assistant physician at Massachusetts General Hospital, Megan Murray, HMS professor of global health and social medicine and collaborators adapted tools from evolutionary biology known as 'phylogenetics.'
The team examined the whole genomes of 116 newly sequenced and 7 previously sequenced strains of TB.
The sample included 47 strains with various levels of resistance to a variety of anti-TB drugs, as well as a group of susceptible strains, to allow the researchers to assess the genetic diversity of TB in the wild.
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.
The small elevation in the resistance levels suggest that resistance is more complex than previously recognized and that likely multiple small mutations may act synergistically to result in full-blown resistance.
The results have been published in Nature Genetics.