Introducing RpsA point mutations 438A and D123A into the chromosome of mycobacterium tuberculosis confirms their role in causing resistance to pyrazinamide

Wanliang Shi; Peng Cui; Hongxia Niu; Shuo Zhang; Tone Tønjum; Bingdong Zhu; Ying Zhang

doi:10.1128/AAC.02681-18

Introducing RpsA point mutations 438A and D123A into the chromosome of mycobacterium tuberculosis confirms their role in causing resistance to pyrazinamide

Wanliang Shi, Peng Cui, Hongxia Niu, Shuo Zhang, Tone Tønjum, Bingdong Zhu, Ying Zhang

Bloomberg School of Public Health

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

10 Scopus citations

Abstract

Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA associated with PZA resistance, but its role in causing PZA resistance has been inconclusive. Here, we introduced the RpsA Δ438A mutation along with the D123A mutation into the Mycobacterium tuberculosis chromosome and demonstrated that these RspA mutations are indeed responsible for PZA resistance.

Original language	English (US)
Article number	e02681-18
Journal	Antimicrobial agents and chemotherapy
Volume	63
Issue number	6
DOIs	https://doi.org/10.1128/AAC.02681-18
State	Published - Jun 2019

Keywords

Drug resistance mechanisms
Mycobacterium tuberculosis
Pyrazinamide
RpsA

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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10.1128/AAC.02681-18

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title = "Introducing RpsA point mutations 438A and D123A into the chromosome of mycobacterium tuberculosis confirms their role in causing resistance to pyrazinamide",

abstract = "Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA associated with PZA resistance, but its role in causing PZA resistance has been inconclusive. Here, we introduced the RpsA Δ438A mutation along with the D123A mutation into the Mycobacterium tuberculosis chromosome and demonstrated that these RspA mutations are indeed responsible for PZA resistance.",

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note = "Funding Information: This work was supported by NIH grant R01AI099512 and the Research Council of Norway INTPART project 261669. Publisher Copyright: Copyright {\textcopyright} 2019 American Society for Microbiology. All Rights Reserved.",

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doi = "10.1128/AAC.02681-18",

language = "English (US)",

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AU - Shi, Wanliang

AU - Cui, Peng

AU - Niu, Hongxia

AU - Zhang, Shuo

AU - Tønjum, Tone

AU - Zhu, Bingdong

AU - Zhang, Ying

N1 - Funding Information: This work was supported by NIH grant R01AI099512 and the Research Council of Norway INTPART project 261669. Publisher Copyright: Copyright © 2019 American Society for Microbiology. All Rights Reserved.

PY - 2019/6

Y1 - 2019/6

N2 - Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA associated with PZA resistance, but its role in causing PZA resistance has been inconclusive. Here, we introduced the RpsA Δ438A mutation along with the D123A mutation into the Mycobacterium tuberculosis chromosome and demonstrated that these RspA mutations are indeed responsible for PZA resistance.

AB - Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA associated with PZA resistance, but its role in causing PZA resistance has been inconclusive. Here, we introduced the RpsA Δ438A mutation along with the D123A mutation into the Mycobacterium tuberculosis chromosome and demonstrated that these RspA mutations are indeed responsible for PZA resistance.

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KW - Pyrazinamide

KW - RpsA

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Introducing RpsA point mutations 438A and D123A into the chromosome of mycobacterium tuberculosis confirms their role in causing resistance to pyrazinamide

Abstract

Keywords

ASJC Scopus subject areas

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