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

Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00430-18. doi: 10.1128/AAC.00430-18. Print 2018 Jul.

Abstract

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 lprG (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.

Keywords: antibiotic resistance; pyrazinamide; tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Drug Resistance, Bacterial / genetics*
  • Lipoproteins / genetics
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Pyrazinamide / analogs & derivatives*
  • Pyrazinamide / pharmacology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Lipoproteins
  • Pyrazinamide
  • pyrazinoic acid