TB Resistance Insights Gleaned From Genome Sequence, Antimicrobial Response Assays

For a paper in PLOS Biology, a University of Oxford team describes a search for genetic variants with ties to the minimum inhibitory concentrations (MIC) of more than a dozen antimicrobial agents — work done through an international consortium effort. Based on whole-genome sequences for more than 10,200 Mycobacterium tuberculosis isolates, along with assays quantifying MIC responses to 13 antimicrobial compounds, the researchers detected variants and genes suspected of influencing responses to the drugs considered. "Use of MIC over binary resistance phenotypes increased sample heritability for the new and repurposed drugs by 26 percent to 37 percent, increasing our ability to detect novel associations," the authors write, adding that "[w]e highlight notable discoveries for each drug and demonstrate the ability of large-scale studies to improve our knowledge of genetic variants associated with antimicrobial resistance in M. tuberculosis."