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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MDPI AG,
2021-01-01T00:00:00Z.
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| Summary: | 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>. |
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| Item Description: | 10.3390/antibiotics10010082 2079-6382 |