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(申请人提供)：复杂的微生物群落与自然界中的所有动植物密切相关：它们影响宿主的进化、生理和生态。微生物在这些共生关系中的具体作用对于在纯培养中生长的那一类微生物来说已经得到了最好的阐明。然而，独立于培养的分子调查的应用表明，这些微生物中的许多还没有培养出来。我们建议通过结合独特的分离和培养方法，从人类微生物群中培养出一组新的生理学微生物--微需氧菌。我们之所以关注微需氧菌，是因为氧气从宿主组织扩散到胃肠道，在组织附近形成了一个微氧区，很可能被微需氧菌定植。由于接近宿主组织，这些微生物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作用的关键。微生物通常是在21%氧气或严格缺氧的环境下分离出来的。虽然这些条件适合培养许多微生物，但微生物在氧气浓度降低的情况下仍能茁壮成长。它们有专门的呼吸酶来在低浓度下获取氧气，因此占据了典型的好氧菌所没有的利基。微需氧菌，包括幽门螺杆菌和弯曲杆菌，占据了许多动物的胃肠道。我们建议从人类微生物群中扩大培养的微氧菌的可用性如下：1)利用微氧环境和新的培养策略从人的胃肠道粘膜中分离微氧菌；2)根据它们在胃肠道中的分布和丰度以及它们在人类群体中的估计流行率来选择具有代表性的微氧菌；3)提供被送去进行基因组测序的代表性菌株的生理特性。微需氧菌的纯培养不仅能够对它们的基因组进行直接测序，而且将成为遗传学、生化和生理学实验检验基因组分析产生的假说的宝贵资源。对这些微生物的生理生态及其对人类的影响的更好的理解，当他们在纯的和有定义的混合培养中被研究时是最容易的。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，以促进包括它们的基因组测序在内的研究。