Despite progress, the mechanisms of action and resistance of pyrazinamide (PZA) are not well understood. Here, we characterized 109 mutants resistant to pyrazinoic acid (POA), the active form of PZA, and found while most (101/109=93%) mutants had panD mutations, and 4 had clpC1 mutation (S91G)(4/109=4%), new mutations in lprG (rv1411c) and rv0521 (4/109=4%), rv3630, rv0010c, ppsC and cyp128 (cytochrome P450 128) were identified, shedding new light on mechanisms of action and resistance of PZA in M. tuberculosis.
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