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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

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（由申请人提供）：人类和其他动物的微生物组是复杂的，人们对其了解甚少，但人们越来越认识到它们以各种各样的方式影响健康。大多数潜在的入侵病原体在接触宿主组织之前，就与复杂的常驻微生物生态系统发生了广泛的相互作用。这些相互作用显然很重要，但由于缺乏易于处理的实验系统，研究起来非常困难。我们最近的创新工作建立了一个实验系统，其中常驻微生物组可以防止某些博德特氏菌的入侵，但不能防止其他非常密切相关的细菌的入侵。我们进一步补充发现，其他博德特氏菌可以取代呼吸道中的常驻微生物群，包括长期慢性定植者。我们在这些密切相关物种的比较生物学和基因组学方面的丰富经验揭示了相关的候选基因，我们的反向遗传学使我们能够开始确定其中一些基因的作用，正如我们的初步结果所述。这些数据开始揭示与常驻微生物群的复杂相互作用是入侵病原体在哺乳动物呼吸道初始定殖的关键方面。该提案将确定参与这种竞争的生态机制，并确定分子机制（基因），在与居民微生物群自然发生相互作用的背景下，确定对入侵病原体的易感性/抗性。