In vitro selected strains harbouring varaints in resistance associated genes
Tuberculosis (TB) treatment is hindered by drug resistance, worsened when drugs are rolled out without adequate diagnostics. We propose using molecular and phenotypic assays to guide diagnostics development prior to market entry. In collaboration with TB Alliance and the European Regimen Accelerator for TB consortium, we applied our strategy to the next-generation diarylquinoline TBAJ-587 and its metabolites.  Long-term in vitro evolutionary assays were performed to identify resistance associated mutations, and Luria-Delbrück fluctuation assays estimated resistance rates. Over 130 mutant clones with elevated MICs were selected, harbouring mutations in genes associated with resistance.
Tuberculosis (TB) treatment is hindered by drug resistance, worsened when drugs are rolled out without adequate diagnostics. We propose using molecular and phenotypic assays to guide diagnostics development prior to market entry. In collaboration with TB Alliance and the European Regimen Accelerator for TB consortium, we applied our strategy to the next-generation diarylquinoline TBAJ-587 and its metabolites.  Long-term in vitro evolutionary assays were performed to identify resistance associated mutations, and Luria-Delbrück fluctuation assays estimated resistance rates. Over 130 mutant clones with elevated MICs were selected, harbouring mutations in genes associated with resistance.
Research Center Borstel Lebniz Lung Center