Genetic analysis in an intractable gut microbe

难治性肠道微生物的遗传分析

• 批准号: 9318512
• 负责人: Raphael H Valdivia
• 金额: $ 23.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318512
• 关键词: Adherence; Affect; Bacteria; Biochemical; Biological Assay; Biology; Bypass; Candidate Disease Gene; Carbon; Chemicals; Complex; Consumption; DNA; DNA Damage; Defect; Diet; Disease; Dissection; Elements; Enzyme Tests; Enzymes; Fatty acid glycerol esters; Frequencies; Future; Gastrointestinal tract structure; Genes; Genetic; Genome; Goals; Growth; Health; High-Throughput DNA Sequencing; Homeostasis; Human; Human Microbiome; Human body; Impairment; Inflammation; Intestines; Libraries; Link; Metabolic; Metabolic Diseases; Methods; Microbe; Molecular; Molecular Genetics; Mucins; Mutagenesis; Mutation; Nutrient; Nutritional; Pathway interactions; Phenotype; Pilum; Polysaccharides; Population; Probiotics; Process; Research; Source; Surface; System; Testing; Work; base; design; gene function; genetic analysis; genetic manipulation; genome annotation; genome sequencing; gut microbiome; improved; in vivo; member; microbial; microbial community; microbiome; mutant; novel; population based; screening; tool; trait; whole genome

ABSTRACT Microbes residing in the vertebrate intestinal tract contribute significantly to host health and disease. The mechanisms by which intestinal bacteria interact with each other and their host are poorly understood because most of these microbes are not amenable to genetic manipulation. We propose to combine phenotypic selection after chemical mutagenesis, and population-based whole genome sequencing to identify genes functionally associated with mucin degradation in the Akkermansia muciniphila, a genetically intractable mucin-degrading gut microbe that has been associated with protection from high-fat induced metabolic disorders and inflammation. The proposed work will seek to identify molecular mechanisms of gut colonization and optimal pro-biotic functions.

摘要 脊椎动物肠道中的微生物对宿主的免疫有重要作用。 健康和疾病。肠道细菌相互作用的机制 它们之间的相互作用以及它们的宿主都知之甚少，因为大多数这些微生物 不适合基因操作。我们建议将联合收割机 化学诱变后的选择和基于群体的全基因组 测序以鉴定在功能上与大肠杆菌中的粘蛋白降解相关的基因， 嗜粘蛋白阿克曼氏菌，一种遗传上难以降解粘蛋白肠道 微生物，已与保护免受高脂肪诱导的代谢 疾病和炎症。拟议的工作将寻求确定分子 肠道定植和最佳益生菌功能的机制。