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This information is not discussed very adequately on a single platform. Additionally, we have discussed the recent technologies that are being used to discover novel resistance mechanisms acquired by Mtb and for exploring novel drugs. The story of intrinsic resistance mechanisms and evolution in Mtb is far from complete. Therefore, we have also discussed intrinsic resistance mechanisms of Mtb and their evolution with time, emphasizing the hope for the development of novel antimycobacterial drugs for effective therapy of tuberculosis.Al