Role of bacteria in development and lifespan of Drosophila melanogaster

细菌在果蝇发育和寿命中的作用

• 批准号: 8010996
• 负责人: WILLIAM W JA
• 金额: $ 24.9万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010996
• 关键词: Affect; Age; Aging; Animals; Bacteria; Bacterial Genes; Behavior; Binding; Complex; Computer Systems Development; Defect; Development; Diet; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Drug Delivery Systems; Exhibits; Genes; Genetic; Genetic Screening; Genomic Library; Genotype; Goals; Health; Human; Immune system; Insecta; Intestines; Lead; Life; Longevity; Maintenance; Mediating; Microbe; Molecular; Muramidase; Nutrient; Organism; Pathway interactions; Phenotype; Probiotics; Property; Reactive Oxygen Species; Research; Role; System; absorption; aging nutrition; antimicrobial peptide; dietary restriction; fitness; fly; gut microbiota; improved; insight; microorganism; microorganism interaction; mutant; nutrition; prevent; research study; response; tool

The mammalian gut harbors a vast association of microorganisms that are critical for optimizing host fitness and health. The interaction of bacteria with their hosts is complex, and ranges from pathogenic to beneficial. Beneficial properties of the intestinal flora include the extraction of nutrients from the host diet, priming ofthe host immune system, and development ofthe gut. The fruit fly, Drosophila melanogaster, is a powerful system for identifying and studying the effects of genes on behavior, aging, and disease. The effects of bacterial colonization ofthe Drosophila gut parallel many ofthe observations made in higher organisms, and the presence of bacteria can extend Drosophila lifespan. Preliminary results have identified a Drosophila mutant that is long-lived only in the presence of bacteria and exhibits distinct gut bacterial colonization. This mutant will be characterized and tools will be developed to study microorganisms harbored in the fly host. In Aim 1, the bacterial species necessary for conferring beneficial effects to fly longevity will be identified. The composition ofthe gut microbiota will be determined as a function of fly age and in response to different nutrient conditions, including under dietary restriction, a manipulation that extends lifespan for a broad range of organisms. Drosophila modulates its gut microbiota using a network of tools including antimicrobial peptides, reactive oxygen species, and acidic lysozymes. These systems will be studied and compared in mutant flies to identify the mechanisms and genes by which hosts affect gut bacterial colonization (Aim 2). To fully characterize host-microbe interactions, a genetic screen will be performed to identify bacterial genes that are critical for colonization of the fly host (Aim 3).

哺乳动物的肠道内有大量的微生物，这些微生物对于优化宿主适应性至关重要 与健康细菌与宿主的相互作用是复杂的，从致病性到致病性， 有利于肠道植物群的有益特性包括从宿主饮食中提取营养物， 启动宿主免疫系统和肠道发育。果蝇是一种 一个强大的系统，用于识别和研究基因对行为、衰老和疾病的影响。的 果蝇肠道细菌定植的影响与许多在更高水平上的观察结果相似， 细菌的存在可以延长果蝇的寿命。初步结果显示 一种果蝇突变体，仅在细菌存在时才能长寿，并表现出明显的肠道细菌 殖民化将对这种突变体进行表征，并开发研究微生物的工具 寄生在苍蝇宿主体内在目标1中，赋予飞行有益效果所必需的细菌种类 将确定寿命。肠道微生物群的组成将被确定为苍蝇年龄的函数 以及响应于不同的营养条件，包括在饮食限制下， 延长了许多生物体的寿命。果蝇使用网络调节其肠道微生物群 包括抗菌肽、活性氧和酸性溶菌酶。这些系统将 在突变果蝇中进行研究和比较，以确定宿主影响肠道的机制和基因 细菌定殖（目的2）。为了充分表征宿主-微生物相互作用，将进行遗传筛选。 进行鉴定对于蝇宿主的定殖至关重要的细菌基因（Aim 3）。