Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 62, Issue 7, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00430-18
Keywords
antibiotic resistance; pyrazinamide; tuberculosis
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Funding
- NIH [AI099512]
- National Science Foundation of China [81772231, 81572046]
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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 had panD mutations and 4 (4%) had clpC1 mutations (S91G), new mutations in 1prG (rv1411c) and rv0521 (n = 4 (4%)), rv3630, rv0010c, ppsC, and cyp128 (cytochrome P450 128) were identified, shedding new light on the mechanisms of action and resistance of PZA in M. tuberculosis.
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