PROGRESSION OF PRIMARY PNEUMONIC PLAGUE

描述（由申请人提供）：鼠疫是由与腺鼠疫相同的微生物引起的，是由鼠疫耶尔森氏菌引起的疾病中最致命的表现。虽然目前世界范围内鼠疫的发病率是低的历史标准，广泛的气溶胶传播和快速疾病进展的可能组合是特别关注的防御生物恐怖主义与Y。鼠疫为了启动哺乳动物感染，Y.鼠疫采用多种机制来干扰宿主的炎症反应，但肺鼠疫的后期阶段以剧烈的炎症为特征。因此，Y.鼠疫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），以便成为呼吸系统的成功病原体。该提案将：（a）探索Y的能力。鼠疫杆菌通过细菌免疫调节基因的靶向缺失来调节原发性肺鼠疫的抗炎和促炎阶段期间的宿主应答，以及（B）鉴定和研究Y.肺鼠疫期间的鼠疫，使用体内DNA微阵列技术。

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.