Comparative Genomics of Oral and Endocarditis Associated Streptococci

描述(申请人提供)：牙菌斑的形成涉及口腔细菌在唾液覆盖的牙齿表面的连续定植。主要的定殖者，包括血链球菌群，戈登链球菌和血链球菌，创造了一种底物，包括病原体在内的后来定殖的物种可以附着在上面。因此，血链球菌不仅影响成熟牙菌斑的组成，还会影响健康或患病的口腔环境的平衡。虽然戈登葡萄球菌和血链球菌主要是口腔的共生成员，但牙科治疗导致的物理分散使它们能够通过血流传播到心脏瓣膜并引起感染性心内膜炎，这是牙科治疗为数不多的潜在致命并发症之一。以前的分类学分类和最近的基于分子的研究表明，血吸虫群体中的多样性水平很高。最近戈登链球菌Challis株和血链球菌SK36株基因组序列的可获得性以及基于基因组的大规模基因组比较工具的开发现在允许对多个分离物进行全基因组检查。这个发现驱动的R21项目的目标是使用基于DNA微阵列的基因发现和多样性方法来检查这些物种的口腔和心内膜炎分离株的基因组谱。其具体目标是：1)利用三个戈登链球菌生物群的代表，构建全基因组鸟枪库比较基因组杂交(SL-CGH)基因发现DNA微阵列，用于识别测序的戈尔登链球菌Challis基因组中不存在的基因和基因组区域；2)构建完整的70聚体寡核苷酸戈登链球菌和血链球菌DNA微阵列，并用它们来检测戈尔登链球菌和血链球菌的代表性口腔、血液和感染性心内膜炎临床分离株的基因组，以确定该物种的基因组多样性。对这些数据的分析将提供关于戈登氏链球菌和血链球菌物种基因组多样性的信息，并提供对这些生物体生物学的洞察。所开发的微阵列工具将具有代表每个物种的各种菌株的基因，将对整个链球菌群体有用。新获得的数据将为功能基因组研究提供基础，以了解这些生物的生物学。 公共卫生：这项建议的目的是测量血液组口腔链球菌的遗传多样性水平，并确定这种多样性是否选择能够引起感染性心内膜炎的特定菌株。

DESCRIPTION (provided by applicant): The formation of dental plaque involves the sequential colonization of oral bacteria on the saliva coated tooth surface. The primary colonizers, which include the sanguis group streptococcal species, S. gordonii and S. sanguis, create a substratum to which later-colonizing species, including pathogens can attach. As a result, the sanguis group streptococci not only influence the composition of mature dental plaque, but also the balance of a healthy or diseased oral environment. Although S. gordonii and S. sanguis are primarily commensal members of the oral cavity, physical dispersion as a result of dental treatment allows them to disseminate via the bloodstream to colonize heart valves and cause infective endocarditis, one of the few potentially lethal complications of dental treatment. Previous taxonomic classification and more recent molecular based studies indicate a high level of diversity among the sanguis group. The recent availability of the S. gordonii strain Challis and S. sanguis strain SK36 genome sequences and development of genomic based tools for large-scale genomic comparisons now allows for a genome wide examination of multiple isolates. The goal of this discovery-driven R21 project is to examine the genomic repertoire of oral and endocarditis isolates from these species using DNA microarray based approaches for gene discovery and diversity. The specific aims are: 1) Using representatives of each of the three S. gordonii biovars, construct whole genome shotgun library comparative genome hybridization (SL-CGH) gene discovery DNA microarrays which will identify genes and genomic regions not present in the sequenced S. gordonii strain Challis genome and 2) Construct comprehensive 70-mer oligonucleotide S. gordonii and S. sanguis DNA microarrays and use them to examine the genomes of representative S. gordonii and S. sanguis oral, blood and infective endocarditis clinical isolates to identify genome diversity within this species. Analysis of these data will provide information on the genomic diversity of the S. gordonii and S. sanguis species and provide insights into the biology of the organisms. The microarray tools developed, which will have genes representative of a variety of strains of each species, will be of use to the entire streptococcal community. The newly available data will provide the basis for functional genomic studies to understand the biology of these organisms. Public Health: The objectives of this proposal are to measure the level of genetic diversity among the sanguis group oral streptococci and determine if this diversity selects for specific isolates capable of causing infective endocarditis.