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The cytochrome bd-type quinol oxidase is important for survival of Mycobacterium smegmatis under peroxide and antibiotic-induced stress
Targeting respiration and ATP synthesis has received strong interest as a new strategy for combatting drug-resistant Mycobacterium tuberculosis. Mycobacteria employ a respiratory chain terminating with two branches. One of the branches includes a cytochrome bc(1) complex and an aa(3)-type cytochrome...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450806/ https://www.ncbi.nlm.nih.gov/pubmed/26015371 http://dx.doi.org/10.1038/srep10333 |
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author | Lu, Ping Heineke, Marieke H. Koul, Anil Andries, Koen Cook, Gregory M. Lill, Holger van Spanning, Rob Bald, Dirk |
author_facet | Lu, Ping Heineke, Marieke H. Koul, Anil Andries, Koen Cook, Gregory M. Lill, Holger van Spanning, Rob Bald, Dirk |
author_sort | Lu, Ping |
collection | PubMed |
description | Targeting respiration and ATP synthesis has received strong interest as a new strategy for combatting drug-resistant Mycobacterium tuberculosis. Mycobacteria employ a respiratory chain terminating with two branches. One of the branches includes a cytochrome bc(1) complex and an aa(3)-type cytochrome c oxidase while the other branch terminates with a cytochrome bd-type quinol oxidase. In this communication we show that genetic inactivation of cytochrome bd, but not of cytochrome bc(1), enhances the susceptibility of Mycobacterium smegmatis to hydrogen peroxide and antibiotic-induced stress. The type-II NADH dehydrogenase effector clofazimine and the ATP synthase inhibitor bedaquiline were bacteriostatic against wild-type M. smegmatis, but strongly bactericidal against a cytochrome bd mutant. We also demonstrated that the quinone-analog aurachin D inhibited mycobacterial cytochrome bd at sub-micromolar concentrations. Our results identify cytochrome bd as a key survival factor in M. smegmatis during antibiotic stress. Targeting the cytochrome bd respiratory branch therefore appears to be a promising strategy that may enhance the bactericidal activity of existing tuberculosis drugs. |
format | Online Article Text |
id | pubmed-4450806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44508062015-06-10 The cytochrome bd-type quinol oxidase is important for survival of Mycobacterium smegmatis under peroxide and antibiotic-induced stress Lu, Ping Heineke, Marieke H. Koul, Anil Andries, Koen Cook, Gregory M. Lill, Holger van Spanning, Rob Bald, Dirk Sci Rep Article Targeting respiration and ATP synthesis has received strong interest as a new strategy for combatting drug-resistant Mycobacterium tuberculosis. Mycobacteria employ a respiratory chain terminating with two branches. One of the branches includes a cytochrome bc(1) complex and an aa(3)-type cytochrome c oxidase while the other branch terminates with a cytochrome bd-type quinol oxidase. In this communication we show that genetic inactivation of cytochrome bd, but not of cytochrome bc(1), enhances the susceptibility of Mycobacterium smegmatis to hydrogen peroxide and antibiotic-induced stress. The type-II NADH dehydrogenase effector clofazimine and the ATP synthase inhibitor bedaquiline were bacteriostatic against wild-type M. smegmatis, but strongly bactericidal against a cytochrome bd mutant. We also demonstrated that the quinone-analog aurachin D inhibited mycobacterial cytochrome bd at sub-micromolar concentrations. Our results identify cytochrome bd as a key survival factor in M. smegmatis during antibiotic stress. Targeting the cytochrome bd respiratory branch therefore appears to be a promising strategy that may enhance the bactericidal activity of existing tuberculosis drugs. Nature Publishing Group 2015-05-27 /pmc/articles/PMC4450806/ /pubmed/26015371 http://dx.doi.org/10.1038/srep10333 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Lu, Ping Heineke, Marieke H. Koul, Anil Andries, Koen Cook, Gregory M. Lill, Holger van Spanning, Rob Bald, Dirk The cytochrome bd-type quinol oxidase is important for survival of Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title | The cytochrome bd-type quinol oxidase is important for survival of
Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title_full | The cytochrome bd-type quinol oxidase is important for survival of
Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title_fullStr | The cytochrome bd-type quinol oxidase is important for survival of
Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title_full_unstemmed | The cytochrome bd-type quinol oxidase is important for survival of
Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title_short | The cytochrome bd-type quinol oxidase is important for survival of
Mycobacterium smegmatis under peroxide and antibiotic-induced stress |
title_sort | cytochrome bd-type quinol oxidase is important for survival of
mycobacterium smegmatis under peroxide and antibiotic-induced stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450806/ https://www.ncbi.nlm.nih.gov/pubmed/26015371 http://dx.doi.org/10.1038/srep10333 |
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