The Microbiota Pathogen Competition

微生物群病原体竞赛

基本信息

批准号：
9291478
负责人：
Eric T Harvill
金额：
$ 28.88万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9291478
关键词：
Address Affect Alleles Animals Antibiotics Area Bacteria Books Bordetella Bordetella pertussis Candidate Disease Gene Chronic Communicable Diseases Comparative Biology Complex Data Ecosystem Exposure to Failure Future Genes Genetic Genome Genomics Goals Health Host Defense Human Human Microbiome Immune In Vitro Individual Infection Infectious Disease Immunology Intuition Invaded Knowledge Libraries Location Lung diseases Mediating Microbe Molecular Mus Mutation Nasal cavity Nature Nose Organism Outcome Pattern Pertussis Predisposition Prevention strategy Process Resistance Respiratory System Respiratory tract structure Role System Text Therapeutic Tissues Translating Virulence Factors Work comparative genomics experience experimental study forward genetics genetic approach in vivo innovation interdisciplinary approach microbiome microbiota microorganism novel strategies pathogen prevent public health relevance respiratory reverse genetics tool weapons

Address Affect Alleles Animals Antibiotics Area Bacteria Books Bordetella Bordetella pertussis Candidate Disease Gene Chronic Communicable Diseases Comparative Biology Complex Data Ecosystem Exposure to Failure Future Genes Genetic Genome Genomics Goals Health Host Defense Human Human Microbiome Immune In Vitro Individual Infection Infectious Disease Immunology Intuition Invaded Knowledge Libraries Location Lung diseases Mediating Microbe Molecular Mus Mutation Nasal cavity Nature Nose Organism Outcome Pattern Pertussis Predisposition Prevention strategy Process Resistance Respiratory System Respiratory tract structure Role System Text Therapeutic Tissues Translating Virulence Factors Work comparative genomics experience experimental study forward genetics genetic approach in vivo innovation interdisciplinary approach microbiome microbiota microorganism novel strategies pathogen prevent public health relevance respiratory reverse genetics tool weapons

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项目摘要

DESCRIPTION (provided by applicant): The microbiomes of humans and other animals are complex and poorly understood, but there is growing appreciation that they affect health in a wide variety of ways. Most potential invading pathogens interact extensively with a complex ecosystem of resident microbes before they can even contact host tissues. These interactions are clearly important, but have been very difficult to study for lack of tractable experimental systems. Our innovative recent work has established an experimental system in which the resident microbiome can protect against invasion by some species of bordetellae but not others that are very closely related. We further made the complementary finding that other bordetellae can displace the resident microbiota from the respiratory tract, including long-term chronic colonizers. Our extensive experience with the comparative biology and genomics of these closely related species has revealed candidate genes involved and our reverse genetics has allowed us to begin to identify roles for some of these, as described in our preliminary results. These data are beginning to reveal the complex interactions with resident microbiota as a critical aspect of an invading pathogen's initial colonization of the mammalian respiratory tract. This proposal will determine the ecological mechanisms involved in this competition, and identify molecular mechanisms (genes), in the context of naturally occurring interactions with resident microbiota that determine susceptibility/resistance to invading pathogens.

描述（由适用提供）：人类和其他动物的微生物群复杂且知识渊博，但人们越来越多地以多种方式影响健康。大多数潜在的入侵病原体在接触宿主组织之前，与居民微生物的复杂生态系统广泛相互作用。这些相互作用显然很重要，但是由于缺乏可拖动的实验系统，很难研究。我们的创新性工作已经建立了一个实验系统，在该系统中，居民微生物组可以防止某些Bordetelae的侵袭，但没有其他非常密切的相关性。我们进一步发现，其他Bordetelae可以从呼吸道（包括长期的慢性殖民者）中取代居民菌群。如我们的初步结果所述，我们对这些密切相关的物种的比较生物学和基因组学的丰富经验揭示了候选基因，我们的反向遗传学使我们能够开始鉴定其中一些角色的作用。这些数据开始揭示与居民微生物群的复杂相互作用，这是入侵病原体对哺乳动物呼吸道初始定植的关键方面。该建议将在与居民微生物群的自然相互作用的背景下确定该竞争中涉及的生态机制，并确定分子机制（基因），这决定了对入侵病原体的敏感性/抗性。