Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i>
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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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/1/82 |
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| author | Liping Liu Hanne Ingmer Martin Vestergaard |
| author_facet | Liping Liu Hanne Ingmer Martin Vestergaard |
| author_sort | Liping Liu |
| collection | DOAJ |
| 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, <i>Staphylococcus aureus</i>. In this study, we aimed to identify intrinsic resistance genes that aid <i>S. aureus</i> in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in <i>S. aureus</i> 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 <i>clpP</i> protease mutant and three mutants with deficiencies in the electron transport chain (<i>menD</i>, <i>hemB</i>, <i>aroC</i>). 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 (<i>recJ</i>, <i>xerC</i> and <i>xseA</i>). Treatment of <i>S. aureus</i> JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of <i>recJ</i>, <i>xerC</i> and <i>xseA</i>, but increased expression of the SOS–stress response genes <i>lexA</i> and <i>recA</i>, suggesting that resveratrol interferes with DNA integrity in <i>S. aureus</i>. 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 <i>S. aureus</i> 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 <i>S. aureus</i>. |
| first_indexed | 2024-03-09T04:35:47Z |
| format | Article |
| id | doaj.art-54afca0a8f564b0fb08e11b90df15172 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T04:35:47Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-54afca0a8f564b0fb08e11b90df151722023-12-03T13:27:33ZengMDPI AGAntibiotics2079-63822021-01-011018210.3390/antibiotics10010082Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i>Liping Liu0Hanne Ingmer1Martin Vestergaard2Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, DenmarkResveratrol 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, <i>Staphylococcus aureus</i>. In this study, we aimed to identify intrinsic resistance genes that aid <i>S. aureus</i> in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in <i>S. aureus</i> 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 <i>clpP</i> protease mutant and three mutants with deficiencies in the electron transport chain (<i>menD</i>, <i>hemB</i>, <i>aroC</i>). 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 (<i>recJ</i>, <i>xerC</i> and <i>xseA</i>). Treatment of <i>S. aureus</i> JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of <i>recJ</i>, <i>xerC</i> and <i>xseA</i>, but increased expression of the SOS–stress response genes <i>lexA</i> and <i>recA</i>, suggesting that resveratrol interferes with DNA integrity in <i>S. aureus</i>. 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 <i>S. aureus</i> 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 <i>S. aureus</i>.https://www.mdpi.com/2079-6382/10/1/82<i>Staphylococcus aureus</i>resveratrolintrinsic resistanceDNA damageSOS response |
| spellingShingle | Liping Liu Hanne Ingmer Martin Vestergaard Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> Antibiotics <i>Staphylococcus aureus</i> resveratrol intrinsic resistance DNA damage SOS response |
| title | Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> |
| title_full | Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> |
| title_fullStr | Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> |
| title_short | Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in <i>Staphylococcus aureus</i> |
| title_sort | genome wide identification of resveratrol intrinsic resistance determinants in i staphylococcus aureus i |
| topic | <i>Staphylococcus aureus</i> resveratrol intrinsic resistance DNA damage SOS response |
| url | https://www.mdpi.com/2079-6382/10/1/82 |
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