Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 associated with pyrazinoic acid/pyrazinamide resistance in mycobacterium tuberculosis

Wanliang Shi, Jiazhen Chen, Shuo Zhang, Wenhong Zhang, Ying Zhang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere00430-18
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number7
DOIs
StatePublished - Jul 1 2018

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Pyrazinamide
Mycobacterium tuberculosis
Cytochrome P-450 Enzyme System
Mutation
pyrazinoic acid

Keywords

  • Antibiotic resistance
  • Pyrazinamide
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

@article{8f10084fe8eb4f21a5e577d943a67d95,
title = "Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 associated with pyrazinoic acid/pyrazinamide resistance in mycobacterium tuberculosis",
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",
author = "Wanliang Shi and Jiazhen Chen and Shuo Zhang and Wenhong Zhang and Ying Zhang",
year = "2018",
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day = "1",
doi = "10.1128/AAC.00430-18",
language = "English (US)",
volume = "62",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
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TY - JOUR

T1 - Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 associated with pyrazinoic acid/pyrazinamide resistance in mycobacterium tuberculosis

AU - Shi, Wanliang

AU - Chen, Jiazhen

AU - Zhang, Shuo

AU - Zhang, Wenhong

AU - Zhang, Ying

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

KW - Antibiotic resistance

KW - Pyrazinamide

KW - Tuberculosis

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U2 - 10.1128/AAC.00430-18

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M3 - Article

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JO - Antimicrobial Agents and Chemotherapy

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