De novo emergence of drug-resistant genetic mutants from antibiotic persistence population

In another parallel project, we have demonstrated that genetic mutants of M. tuberculosis and M. smegmatis, which are resistant to rifampicin and moxifloxacin, emerge de novo from the persistence population generated upon exposure of the cells to the antibiotics for prolonged periods, as in TB treatment regime. The antibiotic persistence cells generate significantly elevated levels of reactive oxygen species (ROS), which in turn inflict genome-wide mutations, to create a pool of antibiotic tolerant mutants. From this pool, antibiotic-resistant genetic mutants emerge in the continued presence of the same antibiotic or any other antibiotic.

We are presently trying to identify the molecular reasons for the generation of high levels of ROS in persistence cells.