Minority Mycobacterium tuberculosis Genotypic Populations as an Indicator of Subsequent Phenotypic Resistance

The authors talk about the minority mycobacterium tuberculosis genotypic populations as an indicator of subsequent phenotypic resistance. Acquired resistance during treatment will remain a principal driver of the extensively drug-resistant tuberculosis epidemic into the foreseeable future. Conventional culture-based phenotypic drug-susceptibility testing (DST) for Mycobacterium tuberculosis (M.tb) as conceived in the 1960s is laborious, scarce in many regions, and too slow for clinical decision-making. Editing commercial molecular TB diagnostic tests provide results within days but can only detect resistant subpopulations greater than 5-65% of the total M.tb population. His team developed a novel targeted next-generation sequencing (NGS) approach (Single Molecule-Overlapping Reads [SMOR]) that is able to discern low-level minority resistant populations between 0.1% and 5% for isoniazid, rifampin, fluoroquinolones, second-line injectables (SLIs), and pyrazinamide. They hypothesized that genotypic microheteroresistance may precede the acquisition of phenotypic drug resistance in clinical practice.