PROGRESSION OF PRIMARY PNEUMONIC PLAGUE

原发性肺鼠疫的进展

• 批准号: 7110540
• 负责人: WYNDHAM W. LATHEM
• 金额: $ 5.04万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110540
• 关键词: infection

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.

描述（由申请人提供）： 肺鼠疫是由与腺鼠疫相同的生物体引起的，是由鼠疫耶尔森氏菌引起的疾病的最致命的表现形式。尽管按照历史标准，目前世界范围内的鼠疫发病率较低，但广泛的气溶胶传播和快速疾病进展的可能结合对于防御鼠疫耶尔森氏菌的生物恐怖活动尤其令人关注。为了引发哺乳动物感染，鼠疫耶尔森氏菌采用多种机制干扰宿主炎症反应，但肺鼠疫的后期阶段以剧烈炎症为标志。因此，鼠疫耶尔森氏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。该提案将：（a）探索鼠疫耶尔森氏菌在原发性肺鼠疫的抗炎和促炎阶段通过有针对性地删除细菌免疫调节基因来调节宿主反应的能力，以及（b）识别和研究早期鼠疫以及使用体内 DNA 微阵列技术研究鼠疫耶尔森氏菌在肺鼠疫期间的晚期转录反应。