Streptococcus gordonii Rgg regulators: gene expression, signaling, oral biofilms

戈登链球菌 Rgg 调节因子：基因表达、信号传导、口腔生物膜

• 批准号: 8825484
• 负责人: M Margaret VICKERMAN
• 金额: $ 19.92万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-20 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8825484
• 关键词: Adhesions; Affect; Algorithms; Back; Bacteria; Binding; Biological; Biological Process; Cells; Chromosomes; Chromosomes, Human, Pair 2; Communities; Competence; Complement; Cytoplasm; DNA; Data; Dental Plaque; Development; Dietary Sucrose; Dietary Sugars; Enzymes; Family; Foundations; Future; Gene Expression; Gene Expression Regulation; Gene Family; Gene Targeting; Genes; Genetic; Genetic Transcription; Genome; Glucans; Glucosyltransferase; Goals; Gram-Positive Bacteria; Growth; Health; Helix-Turn-Helix Motifs; In Vitro; Mediating; Methods; Microbial Biofilms; Molecular; Open Reading Frames; Operon; Peptide Signal Sequences; Peptides; Phase; Phenotype; Pheromone; Play; Process; Promoter Regions; Protein Family; Proteins; Reading; Regulation; Regulator Genes; Role; Salivary; Signal Transduction; Signaling Molecule; Staging; Streptococcus gordonii; Streptococcus pyogenes; Structural Genes; Sucrose; Surface; Tooth structure; Transcription Coactivator; Transcriptional Regulation; Virulence; Water; Work; bacteriocin; base; extracellular; family genetics; genetic regulatory protein; genome sequencing; in vivo; insight; member; mutant; novel; oral bacteria; oral biofilm; promoter; quorum sensing; research study; response; stress tolerance; surface coating; synthetic peptide; tooth surface

DESCRIPTION (provided by applicant): Streptococcus gordonii are pioneer colonizers of dental plaque biofilms. Their accumulation on surfaces is facilitated by glucans synthesized from dietary sucrose by the single extracellular glucosyltransferase (Gtf) enzyme. Regulation of the S. gordonii Gtf structural gene, gtfG, is controlled by the upstream gene, rgg which encodes a transcriptional activator that was the first-identified member of the Rgg family of regulatory proteins. There are seven Rgg-family proteins encoded in the S. gordonii chromosome including the partially characterized RggD which may be involved in glucan-independent biofilm formation. Genome sequence data have shown the widespread occurrence of rgg-family genes among Gram-positive bacteria; data are emerging about shared and unique features of the Rgg family. Rgg proteins usually control transcription of adjacent genes which are involved in various biological functions including colonization, virulence and responses to environmental conditions. Rgg-family proteins can increase or decrease expression of their target genes, often in a growth phase-dependent fashion. Some Rggs control not only the expression of adjacent genes, but act as global regulators acting at promoters of multiple genes located throughout the chromosome as occurs in Streptococcus pyogenes. Our data strongly suggest that S. gordonii Rgg may play similar global regulatory roles affecting expression of genes in addition to gtfG. An exciting recent finding in non-oral streptococcal species is that regulation by some Rgg proteins is mediated by peptide signals that function in a pheromone-like manner and act as quorum sensing molecules to coordinate the bacterial community response. These pheromones are processed from pre-peptides that are often encoded by open reading frames located near rgg genes; these peptides can positively or negatively affect the activity of the cognate Rgg. This newly-discovered mechanism of gene regulation holds intriguing possibilities for exploring novel mechanisms of oral biofilm control. Based upon the emerging evidence for pheromone interactions with Rgg proteins, we hypothesize that Rgg-family regulators may share common mechanisms of action and that as-yet-unidentified peptides may influence the activity of the S. gordonii Rgg proteins. The proposed studies will examine this possibility and provide additional insights into the function of S. gordonii Rgg family proteins via the following Specific Aims: 1) t identify and perform a preliminary characterization of selected S. gordonii target genes controlled by rgg-family determinants by comparing gene expression and resulting phenotypes in parental and mutant strains; 2) to determine if activities of S. gordonii Rgg proteins are influenced by potential pheromone-like peptides by examination of Rgg activity in the presence of both culture filtrates and synthetic peptides. Data will be used as a foundation for a future R01 application. It is hoped that these studies will identify novel facets of oral biofilm formatio that may also provide generally- applicable insights into genetic regulation by Rgg-family proteins in other Gram-positive bacteria.

描述（由申请方提供）：戈登链球菌是牙菌斑生物膜的先驱定植者。它们在表面上的积累是由单一的胞外葡糖基转移酶（Gtf）从膳食蔗糖合成的葡聚糖促进的。S.戈登氏菌Gtf结构基因gtfG受上游基因rgg控制，rgg编码转录激活因子，是调控蛋白Rgg家族的第一个被鉴定的成员。在S. gordonii染色体，包括部分表征的RggD，其可能参与葡聚糖非依赖性生物膜形成。基因组序列数据显示，rgg家族基因在革兰氏阳性菌中广泛存在;关于Rgg家族的共享和独特特征的数据正在出现。Rgg蛋白通常控制邻近基因的转录，这些基因参与各种生物学功能，包括定殖、毒力和对环境条件的响应。Rgg家族蛋白可以增加或减少其靶基因的表达，通常以生长阶段依赖性的方式进行。一些Rggs不仅控制相邻基因的表达，而且作为全局调节剂作用于位于整个染色体中的多个基因的启动子，如化脓性链球菌中所发生的。我们的数据有力地表明，S。戈登Rgg可能发挥类似的全局调节作用，影响基因的表达，除了gtfG。最近在非口腔链球菌物种中的一个令人兴奋的发现是，某些Rgg蛋白的调节是由肽信号介导的，肽信号以信息素样方式起作用，并作为群体感应分子来协调细菌群落反应。这些信息素由前肽加工而成，前肽通常由位于rgg基因附近的开放阅读框编码;这些肽可以积极或消极地影响同源Rgg的活性。这种新发现的基因调控机制为探索口腔生物膜控制的新机制提供了有趣的可能性。基于信息素与Rgg蛋白相互作用的新证据，我们假设Rgg家族调节剂可能具有共同的作用机制，并且尚未鉴定的肽可能影响S.戈登氏菌Rgg蛋白。拟议的研究将检查这种可能性，并提供更多的见解S的功能。gordonii Rgg家族蛋白的研究：1）鉴定并初步表征所选的S. gordonii通过比较亲本和突变株的基因表达和表型来靶向rgg家族决定簇控制的基因; 2）确定S.通过在存在培养物和合成肽的情况下检测Rgg活性，戈登氏菌Rgg蛋白受到潜在的信息素样肽的影响。数据将用作未来R 01应用程序的基础。希望这些研究将鉴定口腔生物膜形成的新方面，其也可以提供对其他革兰氏阳性细菌中Rgg家族蛋白的遗传调节的普遍适用的见解。