Cultivation and Characterization of Microaerobes from the Human Microbiome

人类微生物群中微需氧菌的培养和表征

• 批准号: 7691397
• 负责人: Thomas M Schmidt
• 金额: $ 40.84万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-23 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691397
• 关键词: Address; Aerobic Bacteria; Animals; Attention; Biochemical; Campylobacter; Communities; Complex; Diffuse; Disease; Ecology; Evolution; Gastrointestinal tract structure; Genome; Goals; Harvest; Health; Helicobacter; Human; Human Microbiome; Human body; Laboratories; Microbe; Molecular; Mucous Membrane; Nature; Organism; Oxygen; Physiological; Physiology; Plants; Population; Prevalence; Research; Role; Surveys; Testing; Tissues; base; genetic resource; genome sequencing; improved; microbiome; novel; planetary Atmosphere; public health relevance; research study; respiratory enzyme

DESCRIPTION (provided by applicant): Complex communities of microbes are intimately associated with all plants and animals in nature: they influence the evolution, physiology and ecology of the host. The specific roles of microbes in these symbiotic relationships have been best elucidated for that subset of microbes grown in pure culture. However, the application of cultivation-independent molecular surveys reveals that many of these microbes have yet to be cultivated. We propose to cultivate a physiological subset of novel microbes from the human microbiome - the microaerobes - by incorporating unique approaches to isolation and cultivation. We are focusing on microaerobes because oxygen diffusing into the GI tract from host tissue creates a microoxic zone adjacent to the tissue that is likely to be colonized by microaerobes. As a result of the proximity to the host tissue, these microbes are likely to interact directly with the host and so are key to understanding the role of the microbiome in human health and disease. Microbes are typically isolated under an atmosphere of 21% oxygen or strictly anoxic conditions. While these conditions are suitable for the cultivation of many organisms, microaerobes thrive under reduced concentrations of oxygen. They have specialized respiratory enzymes to harvest oxygen at low concentrations, and as a result occupy niches not available to typical aerobes. Microaerobes, including populations of Helicobacter and Campylobacter, occupy the GI tracts of many animals. We propose to extend the availability of cultured microaerobes from the human microbiome as follows: 1) Exploit microoxic atmospheres and novel cultivation strategies to isolate microaerobes from the mucosa of the human GI tract, 2) Select representative microaerobes based on their distribution and abundance in the GI tract and their estimated prevalence in the human population, 3) Provide a physiological characterization of representative isolates that are sent for genome sequencing. Pure cultures of microaerophiles will not only enable direct sequencing of their genomes, but will be a valuable resource for genetic, biochemical and physiological experiments to test hypotheses generated from genome analyses. An improved understanding of the physiological ecology of these microbes and their impact on humans is most accessible when they are studied in pure and defined mixed cultures. PUBLIC HEALTH RELEVANCE: Complex communities of microbes are intimately associated with the human body. To better understand their role in human health and disease, we proposed to cultivate these microbes in the laboratory to facilitate studies that will include the sequencing of their genomes.

描述（由申请人提供）：复杂的微生物群落与自然界中的所有植物和动物密切相关：它们影响宿主的进化、生理学和生态学。微生物在这些共生关系中的具体作用已经通过纯培养物中生长的微生物子集得到了最好的阐明。然而，独立于培养的分子调查的应用表明，许多微生物尚未被培养。我们建议通过结合独特的分离和培养方法，从人类微生物组中培养出​​新型微生物的生理子集——微需氧菌。我们关注微需氧菌，因为从宿主组织扩散到胃肠道的氧气会在可能被微需氧菌定植的组织附近形成一个微氧区。由于靠近宿主组织，这些微生物很可能直接与宿主相互作用，因此是了解微生物组在人类健康和疾病中的作用的关键。微生物通常在含氧量为 21% 的气氛或严格缺氧的条件下进行分离。虽然这些条件适合许多生物体的培养，但微需氧微生物在氧气浓度较低的情况下却能茁壮成长。它们具有专门的呼吸酶来获取低浓度的氧气，因此占据了典型需氧菌无法利用的生态位。微需氧菌，包括螺杆菌和弯曲杆菌，占据许多动物的胃肠道。我们建议按以下方式扩展人类微生物组中培养的微需氧菌的可用性：1）利用微氧气氛和新的培养策略从人类胃肠道粘膜中分离微需氧菌，2）根据其在胃肠道中的分布和丰度以及它们在人群中的估计患病率来选择代表性微需氧菌，3）提供代表性微需氧菌的生理特征 被送去基因组测序的分离株。微需氧菌的纯​​培养物不仅能够对其基因组进行直接测序，而且将成为遗传、生化和生理实验的宝贵资源，以测试基因组分析产生的假设。当在纯和明确的混合培养物中研究这些微生物时，最容易加深对这些微生物的生理生态学及其对人类的影响的了解。公共卫生相关性：复杂的微生物群落与人体密切相关。为了更好地了解它们在人类健康和疾病中的作用，我们建议在实验室培养这些微生物，以促进包括对其基因组测序在内的研究。