Comparative Genomics of Oral and Endocarditis Associated Streptococci

描述（由申请人提供）：牙菌斑的形成涉及口腔细菌在唾液覆盖的牙齿表面上的连续定植。主要定植者包括血链球菌属、链球菌属gordonii和S.血，创造了一个基质，后来定居的物种，包括病原体可以附着。因此，血链球菌不仅影响成熟牙菌斑的组成，而且影响健康或患病口腔环境的平衡。虽然S. gordonii和S.血液主要是口腔的骨骼成员，由于牙科治疗的结果，血液的物理分散使它们能够通过血流传播，从而在心脏瓣膜上定植，并引起感染性心内膜炎，这是牙科治疗的少数潜在致命并发症之一。先前的分类学分类和最近的分子生物学研究表明，血人组之间的多样性水平很高。最近可用的S。gordonii菌株查利斯和S.血吸虫SK 36株基因组序列的研究和用于大规模基因组比较的基于基因组的工具的开发现在允许对多个分离株进行全基因组检查。这个发现驱动的R21项目的目标是使用基于基因发现和多样性的DNA微阵列方法来检查来自这些物种的口腔和心内膜炎分离株的基因组库。具体目标是：1）使用三个S中的每一个的代表。gordonii biovars，构建全基因组鸟枪文库比较基因组杂交（SL-CGH）基因发现DNA微阵列，将识别基因和基因组区域不存在于测序的S. gordonii菌株查利斯基因组; 2）构建完整的70-mer寡核苷酸S. gordonii和S. sanguis DNA微阵列，并使用它们来检查代表性的S. gordonii和S. sanguis口腔，血液和感染性心内膜炎临床分离株，以确定该物种内的基因组多样性。这些数据的分析将提供关于S. gordonii和S. sanguis物种，并提供深入了解生物体的生物学。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，将用于整个链球菌群落。新获得的数据将为功能基因组研究提供基础，以了解这些生物体的生物学。 公共卫生：本提案的目的是测量口腔链球菌血组之间的遗传多样性水平，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分离株。

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.