Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA
文献类型：期刊论文
| 作者 | Sun, Fei4,5; Liang, Haihua4,5; Kong, Xiangqian2; Xie, Sherrie4,5; Cho, Hoonsik3; Deng, Xin4,5; Ji, Quanjiang4,5; Zhang, Haiyan4,5 ; Alvarez, Sophie1; Hicks, Leslie M.1
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| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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| 出版日期 | 2012-06-05 |
| 卷号 | 109期号:23页码:9095-9100 |
| ISSN号 | 0027-8424 |
| DOI | 10.1073/pnas.1200603109 |
| 文献子类 | Article |
| 英文摘要 | Oxidation sensing and quorum sensing significantly affect bacterial physiology and host-pathogen interactions. However, little attention has been paid to the cross-talk between these two seemingly orthogonal signaling pathways. Here we show that the quorum-sensing agr system has a built-in oxidation-sensing mechanism through an intramolecular disulfide switch possessed by the DNA-binding domain of the response regulator AgrA. Biochemical and mass spectrometric analysis revealed that oxidation induces the intracellular disulfide bond formation between Cys-199 and Cys-228, thus leading to dissociation of AgrA from DNA. Molecular dynamics (MD) simulations suggest that the disulfide bond formation generates a steric clash responsible for the abolished DNA binding of the oxidized AgrA. Mutagenesis studies further established that Cys-199 is crucial for oxidation sensing. The oxidation-sensing role of Cys-199 is further supported by the observation that the mutant Staphylococcus aureus strain expressing AgrAC199S is more susceptible to H2O2 owing to repression of the antioxidant bsaA gene under oxidative stress. Together, our results show that oxidation sensing is a component of the quorum-sensing agr signaling system, which serves as an intrinsic checkpoint to ameliorate the oxidation burden caused by intense metabolic activity and potential host immune response. |
| WOS关键词 | OXYR TRANSCRIPTION FACTOR ; STAPHYLOCOCCUS-AUREUS ; GENE-EXPRESSION ; VIRULENCE ; SARA ; MGRA ; MECHANISM ; PEPTIDES ; MUTATION ; RECEPTOR |
| 资助项目 | National Institutes of Health National Institute of Allergy and Infectious Diseases[AI074658] ; National Institutes of Health National Institute of Allergy and Infectious Diseases[P50GM081892] ; Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease Award[00000000] ; Shanghai Committee of Science and Technology[10410703900] ; 863 Program[SS2012AA021103] ; Chicago Biomedical Consortium[00000000] ; Chicago Community Trust[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000304991100065 |
| 出版者 | NATL ACAD SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278043]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | He, Chuan |
| 作者单位 | 1.Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Indiana Univ Sch Med NW, Dept Microbiol & Immunol, Gary, IN 46408 USA; 4.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 5.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA; |
| 推荐引用方式 GB/T 7714 | Sun, Fei,Liang, Haihua,Kong, Xiangqian,et al. Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109(23):9095-9100. |
| APA | Sun, Fei.,Liang, Haihua.,Kong, Xiangqian.,Xie, Sherrie.,Cho, Hoonsik.,...&He, Chuan.(2012).Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,109(23),9095-9100. |
| MLA | Sun, Fei,et al."Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.23(2012):9095-9100. |
入库方式： OAI收割
来源：上海药物研究所
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