PROGRESSION OF PRIMARY PNEUMONIC PLAGUE

描述（由申请人提供）：肺鼠疫是由鼠疫耶尔森菌引起的最致命的疾病，与淋巴腺鼠疫相同。尽管按历史标准衡量，目前鼠疫在世界范围内的发病率较低，但广泛的气溶胶传播和疾病快速进展的可能结合，对用鼠疫杆菌防御生物恐怖主义尤其值得关注。为了引发哺乳动物感染，鼠疫杆菌采用多种机制干扰宿主的炎症反应，然而肺鼠疫的后期阶段以剧烈炎症为特征。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。本项目将：(a)通过靶向缺失细菌免疫调节基因，探索鼠疫杆菌在原发性肺鼠疫抗炎和促炎阶段调节宿主反应的能力；(b)利用体内DNA微阵列技术，鉴定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.