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Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription

Metrics commonly used to describe antibiotic efficacy rely on measurements performed on bacterial populations. However, certain cells in a bacterial population can continue to grow and divide, even at antibiotic concentrations that kill the majority of cells, in a phenomenon known as antibiotic tole...

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Autores principales: Zhu, Jun-Hao, Wang, Bi-Wei, Pan, Miaomiao, Zeng, Yu-Na, Rego, Hesper, Javid, Babak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181997/
https://www.ncbi.nlm.nih.gov/pubmed/30310059
http://dx.doi.org/10.1038/s41467-018-06667-3
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author Zhu, Jun-Hao
Wang, Bi-Wei
Pan, Miaomiao
Zeng, Yu-Na
Rego, Hesper
Javid, Babak
author_facet Zhu, Jun-Hao
Wang, Bi-Wei
Pan, Miaomiao
Zeng, Yu-Na
Rego, Hesper
Javid, Babak
author_sort Zhu, Jun-Hao
collection PubMed
description Metrics commonly used to describe antibiotic efficacy rely on measurements performed on bacterial populations. However, certain cells in a bacterial population can continue to grow and divide, even at antibiotic concentrations that kill the majority of cells, in a phenomenon known as antibiotic tolerance. Here, we describe a form of semi-heritable tolerance to the key anti-mycobacterial agent rifampicin, which is known to inhibit transcription by targeting the β subunit of the RNA polymerase (RpoB). We show that rifampicin exposure results in rpoB upregulation in a sub-population of cells, followed by growth. More specifically, rifampicin preferentially inhibits one of the two rpoB promoters (promoter I), allowing increased rpoB expression from a second promoter (promoter II), and thus triggering growth. Disruption of promoter architecture leads to differences in rifampicin susceptibility of the population, confirming the contribution of rifampicin-induced rpoB expression to tolerance.
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spelling pubmed-61819972018-10-15 Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription Zhu, Jun-Hao Wang, Bi-Wei Pan, Miaomiao Zeng, Yu-Na Rego, Hesper Javid, Babak Nat Commun Article Metrics commonly used to describe antibiotic efficacy rely on measurements performed on bacterial populations. However, certain cells in a bacterial population can continue to grow and divide, even at antibiotic concentrations that kill the majority of cells, in a phenomenon known as antibiotic tolerance. Here, we describe a form of semi-heritable tolerance to the key anti-mycobacterial agent rifampicin, which is known to inhibit transcription by targeting the β subunit of the RNA polymerase (RpoB). We show that rifampicin exposure results in rpoB upregulation in a sub-population of cells, followed by growth. More specifically, rifampicin preferentially inhibits one of the two rpoB promoters (promoter I), allowing increased rpoB expression from a second promoter (promoter II), and thus triggering growth. Disruption of promoter architecture leads to differences in rifampicin susceptibility of the population, confirming the contribution of rifampicin-induced rpoB expression to tolerance. Nature Publishing Group UK 2018-10-11 /pmc/articles/PMC6181997/ /pubmed/30310059 http://dx.doi.org/10.1038/s41467-018-06667-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhu, Jun-Hao
Wang, Bi-Wei
Pan, Miaomiao
Zeng, Yu-Na
Rego, Hesper
Javid, Babak
Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title_full Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title_fullStr Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title_full_unstemmed Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title_short Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
title_sort rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpob transcription
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181997/
https://www.ncbi.nlm.nih.gov/pubmed/30310059
http://dx.doi.org/10.1038/s41467-018-06667-3
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