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Mitochondria-targeted antioxidants as highly effective antibiotics

Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that is associated with a variety of diseases. Here, we showed that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, exhibited strong antibacterial activity towards Gram-positive Bacillu...

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Autores principales: Nazarov, Pavel A., Osterman, Ilya A., Tokarchuk, Artem V., Karakozova, Marina V., Korshunova, Galina A., Lyamzaev, Konstantin G., Skulachev, Maxim V., Kotova, Elena A., Skulachev, Vladimir P., Antonenko, Yuri N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431119/
https://www.ncbi.nlm.nih.gov/pubmed/28469140
http://dx.doi.org/10.1038/s41598-017-00802-8
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author Nazarov, Pavel A.
Osterman, Ilya A.
Tokarchuk, Artem V.
Karakozova, Marina V.
Korshunova, Galina A.
Lyamzaev, Konstantin G.
Skulachev, Maxim V.
Kotova, Elena A.
Skulachev, Vladimir P.
Antonenko, Yuri N.
author_facet Nazarov, Pavel A.
Osterman, Ilya A.
Tokarchuk, Artem V.
Karakozova, Marina V.
Korshunova, Galina A.
Lyamzaev, Konstantin G.
Skulachev, Maxim V.
Kotova, Elena A.
Skulachev, Vladimir P.
Antonenko, Yuri N.
author_sort Nazarov, Pavel A.
collection PubMed
description Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that is associated with a variety of diseases. Here, we showed that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, exhibited strong antibacterial activity towards Gram-positive Bacillus subtilis, Mycobacterium sp. and Staphylococcus aureus and Gram-negative Photobacterium phosphoreum and Rhodobacter sphaeroides in submicromolar and micromolar concentrations. SkQ1 exhibited less antibiotic activity towards Escherichia coli due to the presence of the highly effective multidrug resistance pump AcrAB-TolC. E. coli mutants lacking AcrAB-TolC showed similar SkQ1 sensitivity, as B. subtilis. Lowering of the bacterial membrane potential by SkQ1 might be involved in the mechanism of its bactericidal action. No significant cytotoxic effect on mammalian cells was observed at bacteriotoxic concentrations of SkQ1. Therefore, SkQ1 may be effective in protection of the infected mammals by killing invading bacteria.
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spelling pubmed-54311192017-05-16 Mitochondria-targeted antioxidants as highly effective antibiotics Nazarov, Pavel A. Osterman, Ilya A. Tokarchuk, Artem V. Karakozova, Marina V. Korshunova, Galina A. Lyamzaev, Konstantin G. Skulachev, Maxim V. Kotova, Elena A. Skulachev, Vladimir P. Antonenko, Yuri N. Sci Rep Article Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that is associated with a variety of diseases. Here, we showed that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, exhibited strong antibacterial activity towards Gram-positive Bacillus subtilis, Mycobacterium sp. and Staphylococcus aureus and Gram-negative Photobacterium phosphoreum and Rhodobacter sphaeroides in submicromolar and micromolar concentrations. SkQ1 exhibited less antibiotic activity towards Escherichia coli due to the presence of the highly effective multidrug resistance pump AcrAB-TolC. E. coli mutants lacking AcrAB-TolC showed similar SkQ1 sensitivity, as B. subtilis. Lowering of the bacterial membrane potential by SkQ1 might be involved in the mechanism of its bactericidal action. No significant cytotoxic effect on mammalian cells was observed at bacteriotoxic concentrations of SkQ1. Therefore, SkQ1 may be effective in protection of the infected mammals by killing invading bacteria. Nature Publishing Group UK 2017-05-03 /pmc/articles/PMC5431119/ /pubmed/28469140 http://dx.doi.org/10.1038/s41598-017-00802-8 Text en © The Author(s) 2017 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
Nazarov, Pavel A.
Osterman, Ilya A.
Tokarchuk, Artem V.
Karakozova, Marina V.
Korshunova, Galina A.
Lyamzaev, Konstantin G.
Skulachev, Maxim V.
Kotova, Elena A.
Skulachev, Vladimir P.
Antonenko, Yuri N.
Mitochondria-targeted antioxidants as highly effective antibiotics
title Mitochondria-targeted antioxidants as highly effective antibiotics
title_full Mitochondria-targeted antioxidants as highly effective antibiotics
title_fullStr Mitochondria-targeted antioxidants as highly effective antibiotics
title_full_unstemmed Mitochondria-targeted antioxidants as highly effective antibiotics
title_short Mitochondria-targeted antioxidants as highly effective antibiotics
title_sort mitochondria-targeted antioxidants as highly effective antibiotics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431119/
https://www.ncbi.nlm.nih.gov/pubmed/28469140
http://dx.doi.org/10.1038/s41598-017-00802-8
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