Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance
文献类型：期刊论文
| 作者 | Sun, Fei3,4; Ding, Yue2; Ji, Quanjiang3,4; Liang, Zhongjie2; Deng, Xin3,4; Wong, Catherine C. L.1; Yi, Chengqi3,4; Zhang, Liang3,4; Xie, Sherrie3,4; Alvarez, Sophie5 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2012-09-18 |
| 卷号 | 109期号:38页码:15461-15466 |
| 关键词 | Ser/Thr kinase PknB transcriptional regulation |
| ISSN号 | 0027-8424 |
| DOI | 10.1073/pnas.1205952109 |
| 文献子类 | Article |
| 英文摘要 | Protein posttranslational modifications (PTMs), particularly phosphorylation, dramatically expand the complexity of cellular regulatory networks. Although cysteine (Cys) in various proteins can be subject to multiple PTMs, its phosphorylation was previously considered a rare PTM with almost no regulatory role assigned. We report here that phosphorylation occurs to a reactive cysteine residue conserved in the staphylococcal accessary regulator A (SarA)/MarR family global transcriptional regulator A (MgrA) family of proteins, and is mediated by the eukaryotic-like kinase-phosphatase pair Stk1-Stp1 in Staphylococcus aureus. Cys-phosphorylation is crucial in regulating virulence determinant production and bacterial resistance to vancomycin. Cell wall-targeting antibiotics, such as vancomycin and ceftriaxone, inhibit the kinase activity of Stk1 and lead to decreased Cys-phosphorylation of SarA and MgrA. An in vivo mouse model of infection established that the absence of stp1, which results in elevated protein Cys-phosphorylation, significantly reduces staphylococcal virulence. Our data indicate that Cys-phosphorylation is a unique PTM that can play crucial roles in bacterial signaling and regulation. |
| WOS关键词 | STAPHYLOCOCCUS-AUREUS ; SIGNAL-TRANSDUCTION ; GLOBAL REGULATOR ; SERINE/THREONINE KINASE ; PSEUDOMONAS-AERUGINOSA ; PHOSPHATE INTERMEDIATE ; TYROSINE-PHOSPHATASE ; ESCHERICHIA-COLI ; GENE-REGULATION ; MGRA |
| 资助项目 | National Institutes of Health National Institute of Allergy and Infectious Diseases[AI074658] ; Bairen Program of the Chinese Academy of Sciences[00000000] ; Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease Award[00000000] ; Shanghai Committee of Science and Technology[10410703900] ; 863 program[2012AA020302] ; Chicago Community Trust[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000309211000078 |
| 出版者 | NATL ACAD SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277942]  |
| 专题 | 药理学第三研究室 |
| 通讯作者 | Lan, Lefu |
| 作者单位 | 1.Scripps Res Inst, San Diego, CA 92121 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA; 4.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 5.Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA |
| 推荐引用方式 GB/T 7714 | Sun, Fei,Ding, Yue,Ji, Quanjiang,et al. Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109(38):15461-15466. |
| APA | Sun, Fei.,Ding, Yue.,Ji, Quanjiang.,Liang, Zhongjie.,Deng, Xin.,...&He, Chuan.(2012).Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,109(38),15461-15466. |
| MLA | Sun, Fei,et al."Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.38(2012):15461-15466. |
入库方式： OAI收割
来源：上海药物研究所
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