Bordetella sp. Versus Microbiota

描述（由申请人提供）：尽管入侵病原体与宿主常驻微生物群之间的相互作用对于许多感染的结果显然是重要的，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对其进行探索。我们最近发现了密切相关的博德特氏菌属病原体与宿主微生物组相互作用的显著差异，这些差异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。支气管败血症有效地定殖小鼠的上呼吸道（URT）（ID 50 <10cfu），并在该过程中取代常驻微生物群落。B。百日咳在人类中引起高度传染性的百日咳，在小鼠中的定植很差（ID50>1000cfu），并且不影响常驻微生物群。测试小鼠的常驻微生物群抑制定殖的假设，我们观察到清除URT的细菌允许B。百日咳杆菌有效定殖（ID50<100）。我们现在通过鉴定可以预防B的特定微生物来扩展这项工作。百日咳定植。该应用程序将1。确定住院医师的能力 抑制B的微生物。小鼠的百日咳定殖，2.确定鼻微生物群和入侵的博德特氏菌之间竞争的生态机制，以及3。确定B.支气管败血症清除URT中的微生物。这种异常强大和易于处理的实验系统将使我们能够研究入侵病原体和宿主驻留微生物群之间的复杂相互作用，以满足分子机制。对这些相互作用的进一步了解可能会为许多其他粘膜病原体的观点提供信息，因为这些病原体没有如此强大的宿主感染实验系统。

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.