() is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator () quorum-sensing system, which allows for the rapid adaptation of to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the system response regulator that binds to the P2 and P3 promoters and upregulates expression. In this study, we reveal that 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 and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the system.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228455PMC
http://dx.doi.org/10.3390/antiox10060841DOI Listing

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