Genetic analysis in an intractable gut microbe

难治性肠道微生物的遗传分析

• 批准号: 9166426
• 负责人: Raphael H Valdivia
• 金额: $ 19.88万
• 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/9166426
• 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; Enzymes; Fatty acid glycerol esters; Frequencies; Future; Gastrointestinal tract structure; Genes; Genetic; Genetic screening method; Goals; Growth; Health; High-Throughput DNA Sequencing; Homeostasis; Human; Human Microbiome; Human body; Inflammation; Intestines; Libraries; Link; Metabolic; Metabolic Diseases; Methods; Microbe; Molecular; Molecular Genetics; Mucins; Mutagenesis; 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 存在于脊椎动物肠道中的微生物对宿主有显着贡献 健康和疾病。肠道细菌与细菌相互作用的机制 人们对彼此及其宿主知之甚少，因为大多数这些微生物 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群体的全基因组 测序鉴定与粘蛋白降解功能相关的基因 Akkermansia muciniphila，一种遗传上难以治愈的粘蛋白降解肠道 与防止高脂肪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 肠道定植机制和最佳益生菌功能。