A Foundation for the Oral Microbiome and Metagenome

口腔微生物组和宏基因组的基础

• 批准号: 7095759
• 负责人: Floyd E Dewhirst
• 金额: $ 65.72万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095759
• 关键词: community; culture; genes; genome; human; infection; information systems; proteins

DESCRIPTION (provided by applicant): The long-term objective of this research is to characterize the cultivable and currently uncultivated microorganisms present in the human oral cavity (microbiome) and all of their genes (metagenome) in order to develop an integrated view of host-microbiome interactions in health and disease. The objectives of this project are to define the unnamed and uncultured oral taxa and to obtain broad metagenomic sequence information that is representative of the phylogenetic diversity of these microorganisms. Recent studies have identified almost 800 species in the oral cavity, of which 35% are named, 11% unnamed but represented by strains, and 54% are unnamed and known only as 16S rRNA sequence phylotypes. There is currently no naming scheme for the unnamed 65% of the microbiome, thus it is nearly impossible to link sequence, phenotypic, prevalence, disease association, and bibliographic information. Aim 1 will make it possible to link these important types of data by naming the unnamed phylotypes, and establishing a curated, Internet-accessible Human Oral Microbiome Database for all prokaryotic oral taxa. There are species from 121 genera in the oral cavity and only minimal genomic information exists for half of these genera. Aim 2 will obtain partial genome sequences for 105 phylogenetically diverse human oral bacteria. Genomic libraries for each species will be constructed and 384 clones will be sequenced from each end, yielding 10%-20% genome coverage for each species. This will add information on 600 genes and proteins for each species and over 60,000 new gene sequences to the oral metagenome. These phylogenetically diverse sequences will facilitate attribution of contigs to specific genera or species in other metagenome projects. Currently, 65% of oral prokaryotes are known only as phylotypes based on 16S rRNA sequences. Meaningful biological characterization requires having living organisms to manipulate on the bench. Aim 3 will identify and deposit reference strains of approximately 200 unnamed oral phylotypes. Strains from phenotypically characterized investigator culture collections will be identified by 16S rRNA sequence analysis and novel reference strains deposited with the American Type Culture Collection. This proposal will significantly enhance our understanding of the human microbiome and allow eventual understanding of its interaction with the host in oral health and disease. This proposal is in response to PA-04-131, Metagenomic Analyses of the Oral Microbiome. This research will help us to understand the several hundred bacteria that live in the human oral cavity and their genes. These bacteria can cause tooth decay, periodontal disease, and infections elsewhere in the body. Knowing more about these many bacteria will allow scientists to develop better methods for treating and preventing oral diseases.

描述（由申请人提供）：这项研究的长期目的是表征人口腔（微生物组）中存在的可栽培和目前未培养的微生物及其所有基因（Metagenome），以发展健康和疾病中宿主 - 微生物组相互作用的综合观点。该项目的目的是定义未命名和未培养的口服分类单元，并获得代表这些微生物的系统发育多样性的广泛宏基因组序列信息。最近的研究已经确定了口腔中的近800种，其中35％的命名为11％，但以菌株为代表，而54％的人未命名，仅被称为16S rRNA序列系统型。目前尚无针对65％的微生物组的命名方案，因此几乎不可能将序列，表型，流行率，疾病关联和书目信息联系起来。 AIM 1将通过命名未命名的系统型，并为所有原核生物口腔分类群建立精选的，互联网访问的人口服微生物组数据库，将这些重要类型的数据链接起来。在口腔中有121个属的物种，其中一半的属仅存在最小的基因组信息。 AIM 2将获得105种系统发育多样的人口腔细菌的部分基因组序列。将构建每个物种的基因组文库，并从每一端测序384个克隆，每种物种的基因组覆盖率为10％-20％。这将添加有关每种物种的600个基因和蛋白质的信息，并将60,000多个新基因序列用于口服元基因组。这些系统发育多样的序列将有助于将重叠群归因于其他元基因组项目中特定属或物种。目前，基于16S rRNA序列，65％的口服原核生物仅被称为系统型。有意义的生物学特征需要使生物体在长凳上操纵。 AIM 3将识别和沉积约200个未命名的口服系统型的参考菌株。通过表型表征的研究者培养物收集的菌株将通过16S rRNA序列分析和与美国类型培养物相同的新参考菌株进行鉴定。该建议将大大增强我们对人类微生物组的理解，并最终了解其与宿主在口腔健康和疾病中的相互作用。 该建议是对PA-04-131的响应，即口服微生物组的元基因组分析。这项研究将帮助我们了解生活在人类口腔及其基因中的数百种细菌。这些细菌会引起人体其他地方其他地方的牙齿腐烂，牙周疾病和感染。了解这些细菌的更多信息将使科学家能够开发出更好的治疗和预防口腔疾病的方法。