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.

抽象的 居住在脊椎动物肠道中的微生物对宿主显着贡献 健康与疾病。肠道细菌相互作用的机制 彼此和他们的宿主对这些微生物的大多数都了解不足 不适合基因操纵。我们建议结合表型 化学诱变后的选择和基于人群的整个基因组 测序以识别与粘蛋白降解功能相关的基因 Akkermansia Muciniphila，一种遗传上棘手的粘蛋白降解肠 与高脂诱导的代谢有关的微生物 疾病和炎症。拟议的工作将寻求识别分子 肠道定植和最佳宝元功能的机制。