Almost all the genomic variation that gives people resistance to 13 of the most common tuberculosis drug treatments have been identified for the first time.
Researchers at The Comprehensive Resistance Prediction for Tuberculosis International Consortium (CRyPTIC) project collected the largest global dataset of clinical M. tuberculosis samples from across the world, with 15,211 samples from 27 countries on five continents.
They used a new quantitative test for drug resistance and a new approach that identified all the genetic changes in a sample of drug-resistant TB bacteria to generate a unique dataset.
This was used to quantify how changes in the genetic code of M. tuberculosis reduce how well different drugs kill these bacteria that cause TB.
They now hope these innovations will lead to improvements as to how TB patients are treated.
Although it is treatable, drug resistance to TB has emerged as a major problem over the past 30 years.
Professor Derrick Crook, professor of microbiology at the University of Oxford, said: “This innovative, large-scale, international collaboration has enabled us to create possibly the most comprehensive map yet of the genetic changes responsible for drug resistance in tuberculosis.”
In a series of nine new preprint manuscripts, the researchers show how the new drug resistance tests should be interpreted and how a massive citizen science project helped to solve the problem.
Manuscripts also include how a new approach to detecting and describing genetic changes in the whole TB genome sequence improved the way genetic changes driving drug resistance can be detected and how these data were used to scan the TB genome sequence for changes not previously known to cause drug resistance.
Prof Crook said: “Our ultimate goal is to achieve a sufficiently accurate genetic prediction of resistance to most anti-tuberculosis drugs, so that whole genome sequencing can replace culture-based DST for TB. This will enable rapid-turnaround near-to-patient assays to revolutionise MDR-TB identification and management.”
The data is freely accessible.
Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis. The CRyPTIC Consortium (2021) medRxiv preprint 18 October 2021
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