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: 7572753
• 负责人: Thomas M Schmidt
• 金额: $ 46.88万
• 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/7572753
• 关键词: Address; Aerobic Bacteria; Animals; Attention; Biochemical Genetics; Campylobacter; Communities; Complex; Condition; 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; Public Health; Research; Role; Surveys; Testing; Tissues; base; genetic resource; genome sequencing; improved; microbiome; novel; planetary Atmosphere; 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、生理和生态。微生物在这些共生关系中的特定作用已经在纯培养中生长的微生物亚群中得到了最好的阐明。然而，与培养无关的分子调查的应用表明，这些微生物中的许多尚未被培养。我们建议通过采用独特的分离和培养方法，从人类微生物组中培养一种新微生物的生理亚群-微需氧菌。我们关注微需氧菌，因为氧气从宿主组织扩散到胃肠道，在组织附近产生了一个微氧区，可能被微需氧菌定殖。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。微生物通常在21%氧气或严格缺氧条件下隔离。虽然这些条件适合于许多生物的培养，但微生物在氧气浓度降低的情况下茁壮成长。它们有专门的呼吸酶来收集低浓度的氧气，因此占据了典型需氧菌无法获得的生态位。微需氧菌，包括螺杆菌和弯曲杆菌，占据许多动物的胃肠道。我们建议从人类微生物组中扩大培养微生物的可用性，如下所示：1）利用微氧气氛和新的培养策略从人胃肠道粘膜中分离微生物，2）基于它们在胃肠道中的分布和丰度以及它们在人群中的估计流行率来选择代表性的微生物，3）提供发送用于基因组测序的代表性分离物的生理表征。微需氧菌的纯培养物不仅能够直接对其基因组进行测序，而且将成为遗传、生物化学和生理学实验的宝贵资源，以检验基因组分析产生的假设。当在纯的和确定的混合培养物中研究这些微生物时，对它们的生理生态学及其对人类的影响的更好理解是最容易的。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，我们建议在实验室中培养这些微生物，以促进包括其基因组测序在内的研究。