PROGRESSION OF PRIMARY PNEUMONIC PLAGUE

描述(申请人提供)：肺鼠疫，由引起腺鼠疫的同一种细菌引起，是由鼠疫耶尔森氏菌引起的疾病的最致命的表现。尽管以历史标准衡量，目前全球鼠疫发病率较低，但广泛的气溶胶传播和疾病的快速发展可能结合在一起，对于防御鼠疫杆菌的生物恐怖主义特别令人担忧。为了启动哺乳动物的感染，鼠疫杆菌使用了许多机制来干扰宿主的炎症反应，但肺炎鼠疫的后期阶段以戏剧性炎症为标志。因此，鼠疫杆菌必须控制并随后适应至少两个不同的感染阶段(抗炎和促炎)，才能成为呼吸系统的成功病原体。这一建议将：(A)探索鼠疫杆菌通过靶向缺失细菌免疫调节基因来调节原发肺鼠疫抗炎和促炎阶段宿主反应的能力，以及(B)利用体内DNA微阵列技术识别和研究鼠疫杆菌在肺鼠疫期间的早期和晚期转录反应。

DESCRIPTION (provided by applicant): Pneumonic plague, caused by the same organism responsible for bubonic plague, is the deadliest manifestation of disease caused by the bacterium Yersinia pestis. Although the current worldwide incidence of plague is low by historical standards, the possible combination of widespread aerosol dissemination and rapid disease progression are of particular concern for defense against bioterrorism with Y. pestis. To initiate mammalian infection, Y. pestis employs a number of mechanisms to interfere with host inflammatory responses, and yet the later stages of pneumonic plague are marked by dramatic inflammation. Thus, Y. pestis must control and subsequently adapt to at least two distinct phases of infection (anti-inflammatory and pro-inflammatory) in order to be a successful pathogen of the respiratory system. This proposal will: (a) explore the ability of Y. pestis to modulate the host response during the anti- and pro-inflammatory phases of primary pneumonic plague via the targeted deletion of bacterial immunomodulatory genes, and (b) identify and study the early and late transcriptional responses by Y. pestis during pneumonic plague using in vivo DNA microarray technology.