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Despite progress, the mechanisms of action and resistance of pyrazinamide (PZA) are not well understood. We characterized 109 mutants resistant to pyrazinoic acid (POA), the active form of PZA, and found that while most (n = 101 [93%]) mutants hadpanD mutations and 4 (4%) hadclpC1 mutations (S91G), new mutations inlprG (rv1411c ) andrv0521 (n = 4 [4%]),rv3630 ,rv0010c ,ppsC , andcyp128 (cytochrome P450 128) were identified, shedding new light on the mechanisms of action and resistance of PZA inM. tuberculosis .

antimicrobial agents and chemotherapy

Identification of Novel Mutations in LprG ( rv1411c ), rv0521 , rv3630 , rv0010c , ppsC , and cyp128 Associated with Pyrazinoic Acid/Pyrazinamide Resistance in Mycobacterium tuberculosis