LuxS-Mediated Quorum Sensing in Streptococcus mutans

LuxS 介导的变形链球菌群体感应

• 批准号: 6693466
• 负责人: ZEZHANG TOM WEN
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693466
• 关键词: Streptococcus mutans; acidity /alkalinity; bacteria infection mechanism; bacterial proteins; biofilm; confocal scanning microscopy; dental plaque; microorganism interaction; northern blottings; proteomics; reporter genes; transcription factor; virulence

DESCRIPTION (provided by applicant): Streptococcus mutans is recognized as the principal etiological agent of dental caries, the most prevalent infectious disease of humans. The ability to metabolize carbohydrates and generate acids, to survive acidic pH and other adverse conditions, and to adhere to and form tenacious biofilms on the tooth surface are believed to be critically associated with the cariogenicity of this human pathogen. Known for its high degree of acid tolerance (aciduricity) and its high capacity to produce acid (acidogenicity), S. mutans lives primarily on the tooth surface at high cell-density in a high diversity ecosystem better known as dental plaque, the structure and composition of which is known to be largely influenced by such factors as the source and availability of nutrients, the pH in the oral cavity and by the ability of the biofilm organisms to adapt to the fluctuations in environmental conditions. Quorum sensing is a cell density--dependent regulatory mechanism that is known to be involved in regulation of a variety of physiologic processes and virulence in both Gram (+) and Gram (-) bacteria. We have recently generated evidence that the S. mutans possesses a gene encoding a functional homologue of the new family of autoinducer synthases (LuxS) that are responsible for production of autoinducers of the quorum sensing system 2, AI-2. This study is designed to yield novel information concerning LuxS-mediated quorum sensing and virulence regulation in S. mutans, which will contribute to our understanding of the pathogenesis of this microorganism and the ecology of the oral flora. The Specific Aims of this proposed study are: 1) to investigate the role of luxS in acid tolerance by S. mutans. By using functional assays, reporter gene fusions, Northern hybridization, and proteomics, we will investigate acid tolerance and its regulation by luxS, and identify novel factors (proteins) that are involved in luxS-regulated acid tolerance responses. 2). To use confocal laser scanning microscopy (CLSM) and mixed, known-species consortia to determine the impact of luxS of S. mutans on bacterial adherence by S. mutans and the inter- and intra-generic interactions between S. mutans and other oral bacteria in terms of biofilm initiation development and structure.

描述（由申请人提供）：变形链球菌被认为是龋齿的主要病原体，龋齿是人类最普遍的传染病。代谢碳水化合物和产生酸的能力，在酸性pH和其他不利条件下生存的能力，以及在牙齿表面粘附和形成坚韧的生物膜的能力，被认为与这种人类病原体的致龋性密切相关。以其高度的耐酸性（耐酸性）和高产酸能力（产酸性）而闻名。变形杆菌主要以高细胞密度生活在牙齿表面上，在高多样性的生态系统中，更好地称为牙菌斑，已知其结构和组成在很大程度上受诸如营养物的来源和可用性、口腔中的pH以及生物膜生物体适应环境条件波动的能力等因素的影响。群体感应是一种细胞密度依赖性调节机制，已知其参与革兰氏（+）和革兰氏（-）细菌的多种生理过程和毒力的调节。我们最近有证据表明，S。变异体具有编码新的自诱导物激酶家族（LuxS）的功能同源物的基因，所述自诱导物激酶家族负责产生群体感应系统2的自诱导物AI-2。本研究旨在获得有关LuxS介导的群体感应和毒力调控的新信息。这将有助于我们了解这种微生物的发病机制和口腔植物群的生态。本研究的具体目的是：1）研究luxS在S.变异体通过使用功能分析，报告基因融合，北方杂交，和蛋白质组学，我们将调查酸耐受性和luxS的调节，并确定新的因素（蛋白质），参与luxS调节的酸耐受性反应。2）。使用共聚焦激光扫描显微镜（CLSM）和混合，已知物种的财团，以确定的影响，luxS的S。变形链球菌对细菌粘附的影响。变形链球菌之间的属间和属内相互作用。变形菌和其它口腔细菌在生物膜起始发育和结构方面的差异。