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
• 负责人: MARK C HERZBERG
• 金额: $ 35.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981418
• 关键词: Adhesions; Adhesives; Bacteria; Bacterial Adhesins; Binding; Biological; Cell Wall; Cell membrane; Cell surface; Cells; Complement; Cues; Data; Dependence; Down-Regulation; Environment; Eukaryotic Cell; Gene Expression; Genes; Genetic Transcription; Gram-Positive Bacteria; Hydroxyapatites; Integrins; Knowledge; MUC5B gene; Mammalian Cell; Measures; Mediating; Membrane Proteins; Microbial Biofilms; Modeling; Molecular Weight; Mucins; Organism; Output; Pathway interactions; Phosphorylation; Proteins; Receptor Signaling; Regulation; Reporting; Saliva; Salivary; Sentinel; Signal Transduction; Specific qualifier value; Specificity; Streptococcus gordonii; Structure; Surface; System; Testing; Work; commensal bacteria; comparative; experimental study; lipoteichoic acid; macromolecule; molecular mass; novel; prevent; protein expression; receptor; response; salivary mucins; sensor; transcriptome; virtual

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了基因的表达。在某些情况下，基因 在与非生物表面接触时，表达会发生变化。我们证明了链球菌 Gordonii是一种典型的革兰氏阳性共生菌，似乎调节表面蛋白 针对具体参与MUC5B的演示。在MUC5B上形成生物膜期间， SGO_0707在细胞壁上的表达及其对SGO_0890和SGO_1487的下调作用 依靠膜内双组分系统(TCS)传感器(SGO_1180)。我们还报道 (初步数据)经过充分研究的成对粘附素，SSPA和SspB(SspAB)，也需要 出现SGO_0707和失去SGO_0890和SGO_1487的信号。多多少少 SspAB在特异性上混杂，与MUC5B结合。因此，SspAB可能作为一种受体诱导 一个由外而内的信号。因为SspAB共价附着在细胞壁上，所以信号传递到细胞 膜可能是由另一个相关的大分子转导的。戈登氏链球菌脂磷壁酸 酸(LTA)结合高分子量的粘蛋白，与细胞壁蛋白相互作用，并穿过 细胞壁，与细胞膜的外层小叶相间。防止S-D-丙氨酸化 Gordonii LTA引起表面蛋白表达的改变。这些数据表明，LTA和 SspAB是MUC5B的共同受体，LTA负责向TCS(SGO_1180)传递信号 和SGO_1181)来改变戈登氏链霉菌的表面蛋白。我们假设， 因此，S.gordonii SspAB与LTA合作作为信号转导的模型 生物膜形成过程中MUC5B的受体。为了测试我们的假设并满足 我们将(1)确定是否同时需要SSPA和SspB；(2) 表明LTA是否作为辅助受体发挥作用；(3)表征反应调节剂SGO_1181 信号和调控；(4)确定表面蛋白呈现的变化是否包括 转录和翻译后机制；以及(5)决定SspAB和 SGO_1180信号通过交叉或平行路径进行比较 转录组分析。为了表征受体信号的输出(目标1-4)，我们将测量 前哨基因的转录(即SSPA、SspB、SGO_0707、SGO_0890、SGO_1487和 SGO_1180)、前哨表面蛋白提呈(即0707、0890、1487)和1180 磷酸化依赖。这些实验将定义戈登链霉菌中由外向内的信号转导。 对特定地表环境线索的反应，这以前被视为 高等有机体的特征。这一知识可能表明某些细菌如何适应变化 当它们必须坚持或死亡的时候，环境。

项目成果

Streptococcus gordonii Type I Lipoteichoic Acid Contributes to Surface Protein Biogenesis.

戈登链球菌 I 型脂磷壁酸有助于表面蛋白的生物合成。

• DOI: 10.1128/msphere.00814-19
• 发表时间: 2019
• 期刊: mSphere
• 影响因子: 4.8
• 作者: Lima,BrunoP;Kho,Kelvin;Nairn,BrittanyL;Davies,JuliaR;Svensäter,Gunnel;Chen,Ruoqiong;Steffes,Amanda;Vreeman,GerritW;Meredith,TimothyC;Herzberg,MarkC
• 通讯作者: Herzberg,MarkC

Uncovering Roles of Streptococcus gordonii SrtA-Processed Proteins in the Biofilm Lifestyle.

揭示戈登链球菌 SrtA 加工蛋白在生物膜生活方式中的作用。

• DOI: 10.1128/jb.00544-20
• 发表时间: 2020
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Nairn,BrittanyL;Lee,GraceT;Chumber,AshwaniK;Steck,PatrickR;Mire,MahmoudO;Lima,BrunoP;Herzberg,MarkC
• 通讯作者: Herzberg,MarkC