...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance
【24h】

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

机译:SarA / MgrA家族转录调节子的蛋白半胱氨酸磷酸化介导细菌毒力和抗生素抗性

获取原文
获取原文并翻译 | 示例
           

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 eukaryotk-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.
机译:蛋白质翻译后修饰(PTM),尤其是磷酸化,大大扩展了细胞调节网络的复杂性。尽管各种蛋白质中的半胱氨酸(Cys)可以经历多个PTM,但其磷酸化以前被认为是罕见的PTM,几乎没有分配调节作用。我们在这里报告说,磷酸化发生在葡萄球菌辅助调节剂A(SarA)/ MarR家族的全球转录调节剂A(MgrA)的蛋白质保守的反应性半胱氨酸残基,并由真核生物样激酶磷酸酶对Stk1-Stp1介导在金黄色葡萄球菌中。半胱氨酸磷酸化对于调节毒力决定因素的产生和细菌对万古霉素的耐药性至关重要。靶向细胞壁的抗生素,例如万古霉素和头孢曲松钠,抑制Stk1的激酶活性并导致SarA和MgrA的Cys磷酸化降低。体内感染小鼠模型确定没有stp1。导致蛋白质Cys-磷酸化水平升高,大大降低了葡萄球菌的毒力。我们的数据表明,Cys磷酸化是独特的PTM,可以在细菌信号传导和调控中发挥关键作用。

著录项

  • 来源
  • 作者单位

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    The Scripps Research Institute, San Diego, CA 92121;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Donald Danforth Plant Science Center, St. Louis, MO 63132;

    Donald Danforth Plant Science Center, St. Louis, MO 63132;

    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;

    Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Ser/Thr kinase PknB; transcriptional regulation;

    机译:Ser / Thr激酶PknB;转录调控;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号