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）：本研究的长期目标是表征人类口腔中存在的可培养和目前未培养的微生物（微生物组）及其所有基因（宏基因组），以便形成宿主与微生物组在健康和疾病中相互作用的综合观点。该项目的目标是定义未命名和未培养的口腔类群，并获得代表这些微生物系统发育多样性的广泛宏基因组序列信息。最近的研究已鉴定出口腔中近 800 个物种，其中 35% 已命名，11% 未命名但以菌株为代表，54% 未命名且仅以 16S rRNA 序列系统发育型为已知。目前还没有针对未命名的 65% 微生物组的命名方案，因此几乎不可能将序列、表型、患病率、疾病关联和书目信息联系起来。目标 1 将通过命名未命名的系统发育型，并为所有原核口腔分类群建立一个精心策划的、可通过互联网访问的人类口腔微生物组数据库，使链接这些重要类型的数据成为可能。口腔中有 121 个属的物种，其中一半的属只存在极少的基因组信息。目标 2 将获得 105 种系统发育多样化的人类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，并对每一端的 384 个克隆进行测序，为每个物种产生 10%-20% 的基因组覆盖率。这将为口腔宏基因组添加每个物种 600 个基因和蛋白质的信息以及超过 60,000 个新基因序列。这些系统发育多样化的序列将有助于将重叠群归因于其他宏基因组项目中的特定属或物种。目前，65% 的口腔原核生物仅被称为基于 16S rRNA 序列的系统发育型。有意义的生物学表征需要在工作台上操纵活的有机体。目标 3 将鉴定并保存大约 200 个未命名的口腔系统型的参考菌株。来自具有表型特征的研究者培养物保藏中心的菌株将通过 16S rRNA 序列分析和保藏于美国典型培养物保藏中心的新参考菌株进行鉴定。该提案将显着增强我们对人类微生物组的了解，并最终了解其在口腔健康和疾病中与宿主的相互作用。 该提案是对 PA-04-131《口腔微生物组宏基因组分析》的回应。这项研究将帮助我们了解生活在人类口腔中的数百种细菌及其基因。这些细菌会导致蛀牙、牙周病和身体其他部位的感染。更多地了解这些细菌将使科学家能够开发出更好的方法来治疗和预防口腔疾病。