A huge analysis looking at thousands of strains of tuberculosis bacteria has found new genes linked to antibiotic resistance – discoveries that could play a crucial role in the future treatment and prevention of tuberculosis, and the fight against drug-resistant bugs. Right now, tuberculosis (TB) can be prevented with a vaccine, and in most cases cured through six months of drug treatments. However, it still claims around 1.5 million lives globally every year – and we don't want that number going in the wrong direction. That's what makes this new study, the largest genome sequencing analysis of Mycobacterium tuberculosis to date, so vital. The threat of a drug-resistant strain of tuberculosis isn't going away anytime soon. "Our study demonstrates the ability of very large-scale studies to substantially improve our knowledge of genetic variants associated with antimicrobial resistance in M. tuberculosis," write the researchers in one of their published papers. In the first of two studies, the team collected and sequenced 12,289 isolates from 23 countries and exposed them to a variety of antimicrobials typically used to treat TB. Of those, more than half were found to be resistant to at least one drug, and 2,129 of those were found to be resistant to the strongest drugs or multiple drugs. In a follow-up experiment based on 10,228 bacterial isolates, the researchers found strains that were tolerant, if not resistant, to each of the 13 antimicrobials tested. Identifying thresholds at which drugs start to affect different strains could determine the most effective dosage to use, or help specialists pick the best courses of treatment. Further analysis identified the 20 most significant genes that provided a degree of resistance to the variants. Scientists will now be able to follow up on the specific genes that have been identified, and study their potential for making tuberculosis resistant to antibiotics. The new information should also help in the treatment of any strain of tuberculosis. "The data compendium is fully open source and it is hoped that it will facilitate and inspire future research for years to come," the researchers write in one of their published papers. The World Health Organization (WHO) wants to improve processes for diagnosing and treating tuberculosis globally, and this study is a part of that. Much more can be done: less than half of drug-resistant tuberculosis cases currently get reported, for example. For antibiotic resistance to be blocked off, scientists need to understand more about these cases, and about the strains that are behind them. The team says the work is particularly important in understanding the effects of what are called new and repurposed drugs (NRDs) which have been recently developed to fight the disease. At the moment, universal drug susceptibility testing is the process used to identify resistant strains, but this requires several weeks and strictly controlled conditions to work. The genetic analysis deployed here promises to be much more effective. "Whole-genome sequencing (WGS) has the potential to reveal the entirety of the M. tuberculosis genetic resistance landscape for any number of drugs simultaneously, while enabling a more rapid turnaround time and reduction in cost," write the researchers. Source
