Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A
<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (<i>agr</i>) quorum-sensing system, which allows for the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/841 |
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| author | Jovana Baković Bess Yi Kun Yu Daniel Silva Maria Baczynska Sew Yeu Peak-Chew Amy Switzer Lynn Burchell Sivaramesh Wigneshweraraj Muralidharan Vandanashree Balasubramanian Gopal Valeriy Filonenko Mark Skehel Ivan Gout |
| author_facet | Jovana Baković Bess Yi Kun Yu Daniel Silva Maria Baczynska Sew Yeu Peak-Chew Amy Switzer Lynn Burchell Sivaramesh Wigneshweraraj Muralidharan Vandanashree Balasubramanian Gopal Valeriy Filonenko Mark Skehel Ivan Gout |
| author_sort | Jovana Baković |
| collection | DOAJ |
| description | <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (<i>agr</i>) quorum-sensing system, which allows for the rapid adaptation of <i>S. aureus</i> to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the <i>agr</i> system response regulator that binds to the P2 and P3 promoters and upregulates <i>agr</i> expression. In this study, we reveal that <i>S. aureus</i> AgrA is modified by covalent binding of CoA (CoAlation) in response to oxidative or metabolic stress. The sites of CoAlation were mapped by liquid chromatography tandem mass spectrometry (LC–MS/MS) and revealed that oxidation-sensing Cys199 is modified by CoA. Surface plasmon resonance (SPR) analysis showed an inhibitory effect of CoAlation on the DNA-binding activity, as CoAlated AgrA had significantly lower affinity towards the P2 and P3 promoters than non-CoAlated AgrA. Overall, this study provides novel insights into the mode of transcriptional regulation in <i>S. aureus</i> and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the <i>agr</i> system. |
| first_indexed | 2024-03-10T11:04:09Z |
| format | Article |
| id | doaj.art-2761bb5322364c82adef8fa706f167cc |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T11:04:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-2761bb5322364c82adef8fa706f167cc2023-11-21T21:14:28ZengMDPI AGAntioxidants2076-39212021-05-0110684110.3390/antiox10060841Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme AJovana Baković0Bess Yi Kun Yu1Daniel Silva2Maria Baczynska3Sew Yeu Peak-Chew4Amy Switzer5Lynn Burchell6Sivaramesh Wigneshweraraj7Muralidharan Vandanashree8Balasubramanian Gopal9Valeriy Filonenko10Mark Skehel11Ivan Gout12Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UKSection of Microbiology, Faculty of Medicine and MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UKSection of Microbiology, Faculty of Medicine and MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UKSection of Microbiology, Faculty of Medicine and MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UKMolecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, IndiaMolecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, IndiaDepartment of Cell Signaling, Institute of Molecular Biology and Genetics, 143 Kyiv, UkraineMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UK<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (<i>agr</i>) quorum-sensing system, which allows for the rapid adaptation of <i>S. aureus</i> to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the <i>agr</i> system response regulator that binds to the P2 and P3 promoters and upregulates <i>agr</i> expression. In this study, we reveal that <i>S. aureus</i> AgrA is modified by covalent binding of CoA (CoAlation) in response to oxidative or metabolic stress. The sites of CoAlation were mapped by liquid chromatography tandem mass spectrometry (LC–MS/MS) and revealed that oxidation-sensing Cys199 is modified by CoA. Surface plasmon resonance (SPR) analysis showed an inhibitory effect of CoAlation on the DNA-binding activity, as CoAlated AgrA had significantly lower affinity towards the P2 and P3 promoters than non-CoAlated AgrA. Overall, this study provides novel insights into the mode of transcriptional regulation in <i>S. aureus</i> and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the <i>agr</i> system.https://www.mdpi.com/2076-3921/10/6/841<i>Staphylococcus aureus</i>quorum-sensingAgrAoxidative stressprotein CoAlationtranscriptional regulation |
| spellingShingle | Jovana Baković Bess Yi Kun Yu Daniel Silva Maria Baczynska Sew Yeu Peak-Chew Amy Switzer Lynn Burchell Sivaramesh Wigneshweraraj Muralidharan Vandanashree Balasubramanian Gopal Valeriy Filonenko Mark Skehel Ivan Gout Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A Antioxidants <i>Staphylococcus aureus</i> quorum-sensing AgrA oxidative stress protein CoAlation transcriptional regulation |
| title | Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A |
| title_full | Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A |
| title_fullStr | Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A |
| title_full_unstemmed | Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A |
| title_short | Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A |
| title_sort | redox regulation of the quorum sensing transcription factor agra by coenzyme a |
| topic | <i>Staphylococcus aureus</i> quorum-sensing AgrA oxidative stress protein CoAlation transcriptional regulation |
| url | https://www.mdpi.com/2076-3921/10/6/841 |
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