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Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus

Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of...

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Autores principales: Liu, Liping, Ingmer, Hanne, Vestergaard, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829806/
https://www.ncbi.nlm.nih.gov/pubmed/33467002
http://dx.doi.org/10.3390/antibiotics10010082
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author Liu, Liping
Ingmer, Hanne
Vestergaard, Martin
author_facet Liu, Liping
Ingmer, Hanne
Vestergaard, Martin
author_sort Liu, Liping
collection PubMed
description Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus.
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spelling pubmed-78298062021-01-26 Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus Liu, Liping Ingmer, Hanne Vestergaard, Martin Antibiotics (Basel) Article Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus. MDPI 2021-01-16 /pmc/articles/PMC7829806/ /pubmed/33467002 http://dx.doi.org/10.3390/antibiotics10010082 Text en © 2021 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
Liu, Liping
Ingmer, Hanne
Vestergaard, Martin
Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title_full Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title_fullStr Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title_full_unstemmed Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title_short Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
title_sort genome-wide identification of resveratrol intrinsic resistance determinants in staphylococcus aureus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829806/
https://www.ncbi.nlm.nih.gov/pubmed/33467002
http://dx.doi.org/10.3390/antibiotics10010082
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