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

doi:10.1128/AAC.00430-18

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

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 language	English (US)
Article number	e00430-18
Journal	Antimicrobial agents and chemotherapy
Volume	62
Issue number	7
DOIs	https://doi.org/10.1128/AAC.00430-18
State	Published - Jul 2018

Keywords

Antibiotic resistance
Pyrazinamide
Tuberculosis

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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10.1128/AAC.00430-18

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Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 associated with pyrazinoic acid/pyrazinamide resistance in mycobacterium tuberculosis. / Shi, Wanliang; Chen, Jiazhen; Zhang, Shuo et al.

In: Antimicrobial agents and chemotherapy, Vol. 62, No. 7, e00430-18, 07.2018.

Research output: Contribution to journal › Article › peer-review

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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",

note = "Funding Information: This study was supported in part by NIH grant AI099512 and the National Science Foundation of China (81772231 and 81572046). Publisher Copyright: Copyright {\textcopyright} 2018 American Society for Microbiology. All Rights Reserved.",

year = "2018",

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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

N1 - Funding Information: This study was supported in part by NIH grant AI099512 and the National Science Foundation of China (81772231 and 81572046). Publisher Copyright: Copyright © 2018 American Society for Microbiology. All Rights Reserved.

PY - 2018/7

Y1 - 2018/7

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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JO - Antimicrobial Agents and Chemotherapy

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

Abstract

Keywords

ASJC Scopus subject areas

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