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The antimycobacterial activity of INH was discovered in , and almost as soon as its activity was published, the first INH-resistant Mycobacterium tuberculosis strains were reported. The second mechanism of INH resistance is a mutation in the promoter region of inhA ct , which in inhA overexpression and le to titration of the drug. Mutations in the inhA open reading frame and promoter region are also the major mechanism of resistance to ETH, found more often in ETH-resistant clinical isolates than mutations in the activator of ETH.

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