Whole genome sequencing of Mycobacterium tuberculosis strains under different conditions

Acquisition of drug resistance in the Mycobacterium tuberculosis (Mtb) necessitates unveiling the potential causes of drug resistance which are yet unknown. To decipher the novel mechanisms we performed genome wide association analysis and identified perturbed DNA repair is one of the leading cause of drug resistance. We generated the gene replacement mutant of mutY, a DNA glycosylase, encoded by Mtb genome. While Rv del mutY and Rv del mutY complement with R262Q did not show the accumulation of direct target mutation and different SNPs in vitro. However, during ex vivo evolution and in the guinea pig lungs Rv del mutY and Rv del mutY complement with R262Q showed the presence of direct target mutation and SNPs.