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Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System
MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD(+) and its bactericidal activity is neutralized by physical interaction with its cognate anti...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291234/ https://www.ncbi.nlm.nih.gov/pubmed/32429486 http://dx.doi.org/10.3390/toxins12050329 |
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author | Ariyachaokun, Kanchiyaphat Grabowska, Anna D. Gutierrez, Claude Neyrolles, Olivier |
author_facet | Ariyachaokun, Kanchiyaphat Grabowska, Anna D. Gutierrez, Claude Neyrolles, Olivier |
author_sort | Ariyachaokun, Kanchiyaphat |
collection | PubMed |
description | MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD(+) and its bactericidal activity is neutralized by physical interaction with its cognate antitoxin MbcA. Therefore, the MbcTA system appears as a promising target for the development of novel therapies against tuberculosis, through the identification of compounds able to antagonize or destabilize the MbcA antitoxin. Here, the expression of the mbcAT operon and its regulation were investigated. A dual fluorescent reporter system was developed, based on an integrative mycobacterial plasmid that encodes a constitutively expressed reporter, serving as an internal standard for monitoring mycobacterial gene expression, and an additional reporter, dependent on the promoter under investigation. This system was used both in M. tuberculosis and in the fast growing model species Mycobacterium smegmatis to: (i) assess the autoregulation of mbcAT; (ii) perform a genetic dissection of the mbcA promoter/operator region; and (iii) explore the regulation of mbcAT transcription from the mbcA promoter (P(mbcA)) in a variety of stress conditions, including in vivo in mice and in macrophages. |
format | Online Article Text |
id | pubmed-7291234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72912342020-06-17 Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System Ariyachaokun, Kanchiyaphat Grabowska, Anna D. Gutierrez, Claude Neyrolles, Olivier Toxins (Basel) Article MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD(+) and its bactericidal activity is neutralized by physical interaction with its cognate antitoxin MbcA. Therefore, the MbcTA system appears as a promising target for the development of novel therapies against tuberculosis, through the identification of compounds able to antagonize or destabilize the MbcA antitoxin. Here, the expression of the mbcAT operon and its regulation were investigated. A dual fluorescent reporter system was developed, based on an integrative mycobacterial plasmid that encodes a constitutively expressed reporter, serving as an internal standard for monitoring mycobacterial gene expression, and an additional reporter, dependent on the promoter under investigation. This system was used both in M. tuberculosis and in the fast growing model species Mycobacterium smegmatis to: (i) assess the autoregulation of mbcAT; (ii) perform a genetic dissection of the mbcA promoter/operator region; and (iii) explore the regulation of mbcAT transcription from the mbcA promoter (P(mbcA)) in a variety of stress conditions, including in vivo in mice and in macrophages. MDPI 2020-05-16 /pmc/articles/PMC7291234/ /pubmed/32429486 http://dx.doi.org/10.3390/toxins12050329 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ariyachaokun, Kanchiyaphat Grabowska, Anna D. Gutierrez, Claude Neyrolles, Olivier Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title | Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title_full | Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title_fullStr | Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title_full_unstemmed | Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title_short | Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System |
title_sort | multi-stress induction of the mycobacterium tuberculosis mbcta bactericidal toxin-antitoxin system |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291234/ https://www.ncbi.nlm.nih.gov/pubmed/32429486 http://dx.doi.org/10.3390/toxins12050329 |
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