Regulation of Surface Protein Presentation on Streptococcus gordonii

戈登链球菌表面蛋白呈递的调节

基本信息

  • 批准号:
    9749996
  • 负责人:
  • 金额:
    $ 35.76万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-01 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

Bacteria alter gene expression while adapting to their environments. In some cases, gene expression changes in response to contact with abiotic surfaces. We show that Streptococcus gordonii, a model Gram-positive commensal bacterium, appears to regulate surface protein presentation in response to specifically engaging MUC5B. During biofilm formation on MUC5B, presentation of SGO_0707 on the cell wall and down-regulation of SGO_0890 and SGO_1487 depend on an intramembrane two-component system (TCS) sensor (SGO_1180). We also report (preliminary data) that the well-studied paired adhesins, SspA and SspB (SspAB), is also required to signal for presentation of SGO_0707 and loss of SGO_0890 and SGO_1487. Somewhat promiscuous in specificity, SspAB binds MUC5B. Hence, SspAB may serve as a receptor to induce an outside-in signal. Since SspAB covalently attaches to the cell wall, the signal to the cell membrane is probably transduced by another associated macromolecule. S. gordonii lipoteichoic acid (LTA) binds high molecular weight mucins, interacts with cell wall proteins, and traverses the cell wall to intercalate with the outer leaflet of the cell membrane. Preventing D-alanylation of S. gordonii LTA causes altered presentation of surface proteins. These data suggest that LTA and SspAB are co-receptors for MUC5B, with LTA serving to transduce a signal to a TCS (SGO_1180 and SGO_1181) to change the surface proteins presented on S. gordonii. We hypothesize, therefore, that S. gordonii SspAB cooperates with LTA to serve as a model signal transducing receptor for MUC5B during biofilm formation. To test our hypothesis and satisfy criteria for an outside-in signaling receptor, we will (1) determine whether both SspA and SspB are required; (2) show whether LTA functions as a co-receptor; (3) characterize response regulator SGO_1181 for signaling and regulation; (4) determine whether the change in surface protein presentation involves transcriptional and post-translational mechanisms; and (5) determine whether SspAB and SGO_1180 signal through intersecting or parallel pathways by performing comparative transcriptome analysis. To characterize the output of receptor signaling (Aims 1-4), we will measure transcription of sentinel genes (i.e., SspA, SspB, SGO_0707, SGO_0890, SGO_1487 and SGO_1180), presentation of sentinel surface proteins (i.e., 0707, 0890, 1487), and 1180 phosphorylation dependence. These experiments will define outside-in signaling in S. gordonii in response to specific surface environmental cues, which had been previously been viewed as a feature of higher organisms. This knowledge could suggest how certain bacteria adapt to changing environments when they must adhere or die.
细菌在适应环境的同时改变基因表达。在某些情况下,基因 与非生物表面接触后表达发生变化。我们发现链球菌 gordonii是一种革兰氏阳性细菌,似乎可以调节表面蛋白 在一个实施方案中,所述抗体可响应于特异性接合MUC 5 B而呈现。在MUC 5 B上的生物膜形成期间, SGO_0707在细胞壁上的呈递以及SGO_0890和SGO_1487的下调 取决于膜内双组分系统(TCS)传感器(SGO_1180)。我们还报告 (初步数据),研究充分的成对粘附素SspA和SspB(SspAB)也需要 SGO_0707呈现以及SGO_0890和SGO_1487丢失的信号。有些 SspAB结合MUC 5 B的特异性混杂。因此,SspAB可以作为受体来诱导 由外向内的信号由于SspAB共价附着于细胞壁,因此向细胞的信号 膜可能是由另一个相关的大分子转导。S.戈登氏脂磷壁 酸(LTA)结合高分子量粘蛋白,与细胞壁蛋白相互作用, 细胞壁与细胞膜的外部小叶插入。防止S. 戈登氏菌LTA导致表面蛋白质的呈递改变。这些数据表明,LTA和 SspAB是MUC 5 B的共受体,LTA用于将信号传递给TCS(SGO_1180 和SGO_1181)改变S. gordonii。我们假设, 因此,S. gordonii SspAB与LTA合作,作为模型信号转导 在生物膜形成过程中MUC 5 B的受体。为了验证我们的假设并满足 由外向内信号受体,我们将(1)确定是否需要SspA和SspB;(2) 显示LTA是否作为共受体起作用;(3)表征响应调节剂SGO_1181, 信号传导和调节;(4)确定表面蛋白呈递的变化是否涉及 转录和翻译后机制;以及(5)确定SspAB和 SGO_1180信号通过交叉或平行途径进行比较 转录组分析。为了表征受体信号传导的输出(目的1-4),我们将测量 哨兵基因的转录(即,SspA、SspB、SGO_0707、SGO_0890、SGO_1487和 SGO_1180),前哨表面蛋白的呈递(即,0707、0890、1487)和1180 磷酸化依赖这些实验将定义S.戈登因 对特定表面环境线索的反应,这在以前被视为一种 高等生物的特征。这些知识可以揭示某些细菌如何适应变化 当他们必须坚持或死亡的环境。

项目成果

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MARK C HERZBERG其他文献

MARK C HERZBERG的其他文献

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{{ truncateString('MARK C HERZBERG', 18)}}的其他基金

A novel, two-armed autotherapy for mucosal infectious diseases
一种针对粘膜感染性疾病的新型双臂自疗法
  • 批准号:
    10229352
  • 财政年份:
    2020
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Surface Protein Presentation on Streptococcus gordonii
戈登链球菌表面蛋白呈递的调节
  • 批准号:
    9391716
  • 财政年份:
    2016
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Surface Protein Presentation on Streptococcus gordonii
戈登链球菌表面蛋白呈递的调节
  • 批准号:
    9783145
  • 财政年份:
    2016
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Surface Protein Presentation on Streptococcus gordonii
戈登链球菌表面蛋白呈递的调节
  • 批准号:
    9313878
  • 财政年份:
    2016
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Surface Protein Presentation on Streptococcus gordonii
戈登链球菌表面蛋白呈递的调节
  • 批准号:
    9981418
  • 财政年份:
    2016
  • 资助金额:
    $ 35.76万
  • 项目类别:
Minnesota Craniofacial Research Training Program
明尼苏达颅面研究培训计划
  • 批准号:
    8500231
  • 财政年份:
    2012
  • 资助金额:
    $ 35.76万
  • 项目类别:
Minnesota Craniofacial Research Training Program
明尼苏达颅面研究培训计划
  • 批准号:
    9081579
  • 财政年份:
    2012
  • 资助金额:
    $ 35.76万
  • 项目类别:
Minnesota Craniofacial Research Training Program
明尼苏达颅面研究培训计划
  • 批准号:
    8337934
  • 财政年份:
    2012
  • 资助金额:
    $ 35.76万
  • 项目类别:
Minnesota Craniofacial Research Training Program
明尼苏达颅面研究培训计划
  • 批准号:
    9389888
  • 财政年份:
    2012
  • 资助金额:
    $ 35.76万
  • 项目类别:
Minnesota Craniofacial Research Training Program
明尼苏达颅面研究培训计划
  • 批准号:
    9406895
  • 财政年份:
    2012
  • 资助金额:
    $ 35.76万
  • 项目类别:

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