Bordetella sp. Versus Microbiota

描述（由申请人提供）：尽管入侵病原体和宿主微生物群之间的相互作用对许多感染的结果显然很重要，但它们仍然知之甚少，很少有实验系统可以在分子机制水平上进行探索。我们最近发现了博德特拉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著差异，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。B. bronchiseptica在小鼠上呼吸道（URT）中有效定植（ID50<10cfu），并在此过程中取代驻留的微生物群。在人类中引起高度传染性百日咳的百日咳杆菌在小鼠中的定植很少（ID50 bb0 1000cfu），并且不影响常驻微生物群。为了验证小鼠常驻微生物群抑制定植的假设，我们观察到清除上呼吸道细菌可使百日咳杆菌有效定植（ID50<100）。我们现在通过确定可以防止百日咳定植的特定微生物扩展了这项工作。这个应用程序将1。定义住院医师的能力

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.