Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A
| Autor: | Amy Switzer, Maria Baczynska, Balasubramanian Gopal, Sivaramesh Wigneshweraraj, Jovana Baković, Muralidharan Vandanashree, Lynn Burchell, Bess Yi Kun Yu, Mark Skehel, Ivan Gout, Valeriy Filonenko, Daniel Silva, Sew Y. Peak-Chew |
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| Přispěvatelé: | Yu, Bess Yi Kun [0000-0002-4619-2226], Switzer, Amy [0000-0003-3604-426X], Wigneshweraraj, Sivaramesh [0000-0002-1418-4029], Gopal, Balasubramanian [0000-0001-9097-5052], Gout, Ivan [0000-0001-9179-8393], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus Physiology 030106 microbiology Clinical Biochemistry Regulator Virulence protein CoAlation RM1-950 medicine.disease_cause Biochemistry quorum-sensing Article 03 medical and health sciences Transcriptional regulation medicine oxidative stress transcriptional regulation Molecular Biology Transcription factor Chemistry Promoter Cell Biology biochemical phenomena metabolism and nutrition Cell biology AgrA Quorum sensing Response regulator 030104 developmental biology Therapeutics. Pharmacology |
| Zdroj: | Antioxidants, Vol 10, Iss 841, p 841 (2021) Antioxidants Volume 10 Issue 6 |
| ISSN: | 2076-3921 |
| Popis: | Staphylococcus aureus (S. aureus) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (agr) quorum-sensing system, which allows for the rapid adaptation of S. aureus to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the agr system response regulator that binds to the P2 and P3 promoters and upregulates agr expression. In this study, we reveal that S. aureus 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 S. aureus and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the agr system. |
| Databáze: | OpenAIRE |
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