GENOME SEQUENCE OF STREPTOCOCCUS SOBRINUS

该项目的目标是确定远缘链球菌6715的基因组序列，这是一种与龋齿形成有关的口腔细菌。远缘链球菌是一种早期定植的口腔细菌，它对牙齿表面的黏附以及与其他类型的细菌聚集形成菌斑起着重要作用。结合到覆盖牙齿表面的宿主衍生蛋白质层允许远缘链球菌和相关链球菌启动口腔定植。远缘链霉菌的高度酸尿性使其能够在环境中的pH降低时继续产酸。由于酸的产生对牙釉质中磷酸钙的释放和随后的龋齿形成非常重要，远缘链球菌这种独特的持续降低环境pH的能力对于全面了解牙周病具有重要意义。全基因组测序的最新进展使获得远缘链霉菌6715的2.20MbP全基因组序列成为可能。完整的序列和一组互补的克隆将为理解远缘链霉菌的生物学提供巨大的资源。拟议的项目将包括：i)从远缘链霉菌6715构建随机的中小插入质粒库和大插入BAC文库；ii)对大约21,333个小插入和中插入克隆的两端进行测序；iii)对一组BAC克隆的末端进行测序，以提供对重叠群进行排序的基因组支架，并减少缝隙关闭所需的工作量；以及iv)基因组的组装和注释，以确定结构特征，并根据数据库相似性搜索将基因功能角色分配给开放阅读框。这一全基因组测序项目将补充正在进行的肺炎链球菌、化脓性链球菌、无乳链球菌和变形链球菌的测序和分析，并将允许识别这些生物特有的因素。该项目还将有助于了解远缘链霉菌成功定植口腔的致病机制。该项目产生的数据将存入公共数据库，包括TIGR万维网网站。此外，用于生成完整基因组序列的文库和重叠的BAC克隆集将向研究界提供。

The goal of this project is to determine the genome sequence of Streptococcus sobrinus 6715, an oral bacterium associated with the formation of dental caries. Streptococcus sobrinus is one of the early colonizing oral bacteria that play a significant role in adherence to the tooth surface, and also in coaggregations with other types of bacteria to form plaque. Binding to the host derived protein layer that covers the tooth surface allows S. sobrinus and related streptococci to inititate colonization of the oral cavity. The highly aciduronic nature of S. sobrinus allows the organism to continue producing acid as the pH in its environment lowers. As acid production is important to the release of calcium phosphates from the tooth enamel, and the subsequent formation of caries, this unique ability of S. sobrinus to continue reducing environmental pH is significant to a complete understanding of periodontal disease. Recent advances in whole genome sequencing now make it possible to obtain the complete genome sequence of the 2.20 Mbp genome of S. sobrinus 6715. The complete sequence along with a complementary set of clones will provide a tremendous resource in being able to understand the biology of S. sobrinus. The proposed project will encompass: i) construction of random small and medium insert plasmid libraries and a large insert BAC library from S. sobrinus 6715; ii) sequencing of both ends of approximately 21,333 small and medium insert clones; iii) sequencing the ends of a set of BAC clones clones to provide a genome scaffold to order contigs, and reduce the effort needed for gap closure; and iv) assembly and annotation of the genome to identify structural features, and assign gene functional roles to open reading frames, based on database similarity searches. This whole genome sequencing project will complement the ongoing sequencing and analysis of the related streptococci Streptococcus pneumoniae, S. pyogenes, S. agalactiae, and S. mutans, and will allow for the identification of factors unique to these organisms. The project will also allow for the understanding of the pathogenic mechanisms used by S. sobrinus to successfully colonize the oral cavity. The data generated from this project will be deposited in public databases, including the TIGR World Wide Web Site. In addition, the libraries and overlapping BAC clone sets used to generate the complete genome sequence will be made available to the research community.