Bordetella sp. Versus Microbiota

博德特氏菌属

基本信息

批准号：
8896095
负责人：
Eric T Harvill
金额：
$ 37.68万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8896095
关键词：
Affect Animal Diseases Animal Model Animals Antibiotic Therapy Antibiotics Bacteria Behavior Biological Assay Biological Models Biology Bordetella Bordetella pertussis Characteristics Communicable Diseases Complex Controlled Study Data Disease Distant Dose Employee Strikes Evolution Failure Genes Genetic Genome Genomics Health Human Immune In Vitro Individual Infection Invaded Laboratory Animals Laboratory Infection Libraries Ligands Light Location Measures Mediating Microbe Modeling Molecular Mus Mutation Nasal cavity Nature Nose Organism Outcome Pathology Pattern Pertussis Predisposition Process Respiratory System Respiratory tract structure Role Specific qualifier value Specificity System Testing Translating Upper respiratory tract Virulence Factors Work base body system human disease improved in vivo microbial community microbiome microorganism mutant novel strategies pathogen positional cloning prevent receptor research study respiratory success tool transmission process weapons

项目摘要

DESCRIPTION (provided by applicant): Although the interactions between invading pathogens and the host's resident microbiota are clearly important to the outcome of many infections, they remain poorly understood with few experimental systems in which they can be explored at a molecular mechanistic level. We have recently identified striking differences between closely related pathogens of the genus Bordetella in their interactions with host microbiome that can explain important aspects of their biology, including host specificity and pathology. B. bronchiseptica efficiently colonizes the upper respiratory tracts (URT) of mice (ID50<10cfu) and displaces the resident microflora in the process. B. pertussis, which causes highly contagious Whooping Cough in humans, poorly colonizes mice (ID50>1000cfu) and does not affect resident microbiota. Testing the hypothesis that resident microbiota of mice inhibit colonization, we observed that clearing the URT of bacteria allows B. pertussis to efficiently colonize (ID50<100). We have now extended this work by identifying specific microorganisms that can prevent B. pertussis colonization. This application will 1. Define the ability of resident microorganism(s) to inhibit B. pertussis colonization of mice, 2. Identify ecological mechanisms of competition amongst nasal microbiota and invading bordetellae, and 3. Determine the molecular mechanisms by which B. bronchiseptica clears microflora from the URT. This exceptionally powerful and tractable experimental system will allow us to study the complex interactions between invading pathogen and host resident microbiota to satisfying molecular mechanisms. Improved understanding of these interactions is likely to inform views of the many other mucosal pathogens for which there is not such a powerful host infection experimental system.

描述（由申请人提供）：尽管入侵病原体与宿主体内微生物群之间的相互作用对于许多感染的结果显然很重要，但人们对它们的了解仍然很少，很少有实验系统可以在分子机制水平上对其进行探索。我们最近发现了博德特氏菌属密切相关的病原体在与宿主微生物组相互作用方面的显着差异，这可以解释其生物学的重要方面，包括宿主特异性和病理学。支气管败血芽孢杆菌有效定植于小鼠的上呼吸道 (URT) (ID50<10cfu)，并在此过程中取代常驻微生物群。百日咳博德特氏菌会在人类中引起高度传染性的百日咳，但它在小鼠中的定殖能力较差（ID50>1000cfu），并且不会影响常驻微生物群。测试小鼠常驻微生物群抑制定植的假设，我们观察到清除 URT 中的细菌可以使百日咳博德特氏菌有效定植（ID50<100）。现在，我们通过鉴定可以预防百日咳博德特氏菌定植的特定微生物来扩展这项工作。该申请将 1. 定义居民的能力抑制百日咳博德特氏菌在小鼠体内定植的微生物，2. 确定鼻腔微生物群和入侵博德特氏菌之间竞争的生态机制，以及 3. 确定支气管败血博德特氏菌清除 URT 微生物群的分子机制。这个异常强大且易于处理的实验系统将使我们能够研究入侵病原体与宿主微生物群之间复杂的相互作用，以满足分子机制。对这些相互作用的更好的理解可能会为许多其他粘膜病原体的观点提供信息，而这些病原体还没有如此强大的宿主感染实验系统。