LuxS-Mediated Quorum Sensing in Streptococcus mutans

描述(申请人提供)：变形链球菌被认为是龋病的主要病原体，龋病是人类最常见的传染病。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，以及在牙齿表面附着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。变形链球菌以其高度的耐酸性(耐酸性)和高产酸能力(产酸性)而闻名，主要以高细胞密度生活在高度多样性的生态系统中，即牙菌斑，其结构和组成在很大程度上受到营养物质的来源和可获得性、口腔中的pH值以及生物膜生物适应环境条件波动的能力等因素的影响。群体感应是一种依赖于细胞密度的调节机制，已知参与调节革兰氏()和革兰氏(-)细菌的各种生理过程和毒力。我们最近获得的证据表明，变形链球菌拥有一个编码新的自诱导合酶家族(LuxS)的功能同源基因，该家族负责产生群体感应系统2，AI-2的自诱导子。本研究旨在获得关于LuxS介导的变形链球菌群体感应和毒力调节的新信息，这将有助于我们理解这种微生物的发病机制和口腔菌群的生态学。本研究的具体目的是：1)研究LuxS在变形链球菌耐酸性中的作用。通过功能分析、报告基因融合、Northern杂交和蛋白质组学，我们将研究耐酸性及其受LuxS的调控，并寻找参与LuxS调节耐酸反应的新因子(蛋白质)。2)。目的：利用激光共聚焦扫描显微镜(CLSM)和已知的混合菌种联合体，从生物膜的形成、发展和结构的角度，确定变形链球菌的LuxS对变形链球菌的细菌黏附的影响，以及变形链球菌与其他口腔细菌之间的属间和属内相互作用。

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.