As limited studies have been conducted in high DR TB burden countries to characterize PZA resistance, this nationwide investigation of 2,207 MTB isolates aimed to explore the spectrum of mutations that confer resistance to PZA, assess the current prevalence of PZAR in India, and most importantly, evaluate the diagnostic potential of sequencing pncA, rpsA, panD and clpC1 genes after assessing their roles in PZAR. This evidence concerns the gene RPSA and tuberculosis.