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: 7585799
• 负责人: Floyd E Dewhirst
• 金额: $ 74.53万
• 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/7585799
• 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种植的和目前未种植的 存在于人类口腔中的微生物(微生物组)及其所有基因(元基因组) 发展健康和疾病中宿主-微生物组相互作用的综合观点。这样做的目的是 项目是定义未命名和未培养的口腔分类群，并获得广泛的元基因组序列 代表这些微生物系统发育多样性的信息。最新研究 在口腔中发现了近800种物种，其中35%已命名，11%未命名，但 其中54%未命名，仅为16S rRNA序列系统型。的确有 目前还没有对未命名的65%的微生物组进行命名的方案，因此几乎不可能将 序列、表型、流行率、疾病关联和书目信息。目标1会成功的 通过命名未命名的系谱类型，并建立一个 所有原核生物口腔分类群的可供互联网访问的人类口腔微生物组数据库。确实有 口腔中有121个属的物种，其中一半只有很少的基因组信息 属。目的2将获得105种不同系统发育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，并从每一端对384个克隆进行测序， 使每个物种的基因组覆盖率达到10%-20%。这将增加关于600个基因和蛋白质的信息 为每个物种和超过60,000个新的基因序列的口腔元基因组。从亲缘关系上讲 不同的序列有助于将重叠群归属于其他元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16S rRNA序列的系统分类。 有意义的生物学特征需要有活的有机体在工作台上进行操作。目标3 将鉴定和保存大约200个未命名的口腔系统型的参考菌株。菌株来自 表型特征的调查者培养样本将通过16S rRNA序列进行鉴定 保存在美国典型培养库中的分析和新的参考菌株。这项提议将 极大地增强了我们对人类微生物组的了解，并使我们最终能够理解它的 与宿主在口腔健康和疾病方面的互动。这项建议是对PA-04-131的回应， 口腔微生物组的基因组学分析。 这项研究将有助于我们了解生活在人类口腔中的数百种细菌和 他们的基因。这些细菌会导致龋齿、牙周病和其他地方的感染。 尸体。更多地了解这些细菌将使科学家能够开发出更好的治疗方法 预防口腔疾病。