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Redox regulation of the quorum-sensing transcription factor agra by coenzyme a

Baković, J; Yu, BYK; Silva, D; Baczynska, M; Peak-Chew, SY; Switzer, A; Burchell, L; ... Gout, I; + view all (2021) Redox regulation of the quorum-sensing transcription factor agra by coenzyme a. Antioxidants , 10 (6) 10.3390/antiox10060841. Green open access

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Abstract

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.

Type: Article
Title: Redox regulation of the quorum-sensing transcription factor agra by coenzyme a
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/antiox10060841
Publisher version: http://dx.doi.org/10.3390/antiox10060841
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Staphylococcus aureus; quorum-sensing; AgrA; oxidative stress; protein CoAlation; transcriptional regulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10129225
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