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: 7796933
• 负责人: Floyd E Dewhirst
• 金额: $ 18.72万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7796933
• 关键词: Actinobacillus actinomycetemcomitans; American Type Culture Collection; Animal Model; Appointment; Bacteria; Bibliography; Biochemical; Biological; Blast Cell; Brain; Clinical; Collection; Communicable Diseases; Communities; Computer Simulation; Data; Databases; Dental; Dental caries; Deposition; Disease; Disease Association; Ear; Environment; Faculty; Family; Foundations; Genbank; Gene Proteins; Genes; Genetic; Genome; Genomic Library; Genomics; Goals; Habitats; Health; Heart; Host Defense Mechanism; Human; Human Microbiome; Infection; Infectious Diseases Research; Institutes; Institution; Internet; Investigation; Joints; Knowledge; Laboratories; Lead; Libraries; Life; Link; Liver; Lung; Medicine; Metagenomics; Methods; Microbe; Microbiology; Molecular; Molecular Analysis; Mouth Diseases; NIH Program Announcements; Names; National Institute of Dental and Craniofacial Research; Nucleic Acids; Online Systems; Oral; Oral cavity; Oral health; Organism; Pathologic; Periodontal Diseases; Phylogenetic Analysis; Porphyromonas gingivalis; Prevalence; Principal Investigator; Prokaryotic Cells; Proteins; Proteobacteria; PubMed; Publications; Qualifying; Research; Research Personnel; Resources; Ribosomal RNA; Scheme; Scientist; Sequence Analysis; Side; Site; Streptococcus mutans; Surveys; Systemic infection; Taxon; Taxonomy; Trees; United States; base; bone; cost; experience; genome sequencing; innovation; member; metagenomic sequencing; microbial; microbiome; microorganism; novel; oral bacteria; oral infection; oral microbiome; prevent; programs; research study; response; tool; vector

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.

这项研究的长期目标是描述可栽培和目前未栽培的 存在于人类口腔中的微生物（微生物组）及其所有基因（宏基因组）， 发展健康和疾病中宿主-微生物组相互作用的综合观点。这一目标 项目的目的是确定未命名和未培养的口腔分类群，并获得广泛的宏基因组序列 这些微生物的系统发育多样性的代表信息。最近的研究 已经确定了口腔中的近800种物种，其中35%已命名，11%未命名， 以菌株为代表，54%是未命名的，仅以16 S rRNA序列命名。有 目前，65%未命名的微生物组没有命名方案，因此几乎不可能将其联系起来。 序列、表型、患病率、疾病关联和书目信息。目标1会成功的 通过命名未命名的数据类型，并建立一个 所有原核生物口腔分类群的互联网可访问的人类口腔微生物组数据库。有 口腔中的121个属中的121个物种，并且对于这些物种中的一半，仅存在最少的基因组信息 属目的2获得105株不同遗传背景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，并从每个末端测序384个克隆， 每个物种的基因组覆盖率为10%-20%。这将增加600个基因和蛋白质的信息 以及超过60，000个新的基因序列。这些遗传学 不同的序列将有助于将重叠群归属于其他宏基因组中的特定属或种 项目目前，65%的口腔原核生物仅被认为是基于16 S rRNA序列的哺乳动物。 有意义的生物表征需要有活的生物体在实验台上进行操作。目标3 将鉴定并存款大约200种未命名的口腔粘膜炎类型的参考菌株。菌株 表型表征的研究者培养物收集物将通过16 S rRNA序列进行鉴定 分析和新的参考菌株保藏在美国典型培养物保藏中心。这项建议会 显著提高我们对人类微生物组的理解，并允许最终了解其 口腔健康和疾病与宿主的相互作用。本提案是对PA-04-131的回应， 口腔微生物组的宏基因组分析。 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， 他们的基因这些细菌会导致蛀牙，牙周病和其他地方的感染。 身体了解更多关于这些细菌将使科学家开发更好的方法来治疗 和预防口腔疾病。