Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A.
Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A.
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DOI：
10.3390/antiox10060841
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发表时间：
2021-05-25
期刊：
影响因子：
--
通讯作者：
Gout I
中科院分区：
文献类型：
--
作者：
Baković J;Yu BYK;Silva D;Baczynska M;Peak-Chew SY;Switzer A;Burchell L;Wigneshweraraj S;Vandanashree M;Gopal B;Filonenko V;Skehel M;Gout I
金黄色葡萄球菌(S.金黄色葡萄球菌）是一种具有显著毒力和抗生素抗性的侵袭性机会致病菌。这些特征部分归因于辅助基因调节子（agr）群体感应系统，该系统允许S.金黄色葡萄球菌对环境的改变，从而促进毒力和致病性的发展。AgrA是与P2和P3启动子结合并上调agr表达的agr系统应答调节剂。在本研究中，我们发现S.金黄色葡萄球菌AgrA通过CoA的共价结合（CoAlation）来修饰以响应氧化或代谢应激。通过液相色谱-串联质谱（LC-MS/MS）对CoAlation位点进行了分析，结果表明CoA修饰了氧化传感器Cys 199。表面等离子体共振（SPR）分析显示CoAlation对DNA结合活性有抑制作用，因为CoAlated AgrA对P2和P3启动子的亲和力显著低于非CoAlated AgrA。总之，本研究为进一步研究S.并进一步阐明了AGR系统的群体感应和氧化感应作用之间的联系。
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.
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