Perpetuation of Francisella tularensis

土拉弗朗西斯菌的永存

• 批准号: 7350858
• 负责人: Sam R Telford
• 金额: $ 37.42万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350858
• 关键词: Acute; Animals; Biological; Biology; Competence; Cyst; Desiccation; Disease Outbreaks; Environment; Fever; Francisella tularensis; Genotype; Goals; Hematogenous; Histopathology; Immunohistochemistry; In Vitro; Infection; Inherited; Island; Lateral; Maintenance; Measures; Minisatellite Repeats; Mus; Nature; Oryctolagus cuniculus; Outcome; Polymerase Chain Reaction; Prevalence; Protozoa; Pulmonary Pathology; Rattus; Resistance; Risk; Rodent; Simulate; Site; Stress; Structure; Testing; Ticks; Tissues; Tularemia; Variant; Virulence; Virulent; Water; base; cytokine; enzootic; epizootic; genetic variant; human disease; mRNA Expression; pathogen; transmission process; vector

Francisella tularensis is the causative agent of tularemia, an acute febrile infection with variable presentation and outcomes. Although the agent is said to be maintained in nature by cycles involving ticks and rodents or rabbits, its great infectivity and presumptiveenvironmental stability suggestsother modes of perpetuation. Our longterm goal is to determine the proximal determinants of risk for outbreaksof tularemia, and in particular,how the agent is maintained between epizootics. The specific hypothesis is that multiple modes of transmission are facilitated by a metapopulation structure of genetic variants within an enzootic focus; certain variants may be better adaptedto ticks as opposed to environmental reservoirs. We base our hypothesis on our investigationof the ongoing pneumonic tularemia outbreak on Martha's Vineyard, wherein we have found (1) that 11 F. tularensis variants circulate in our island study sites; and (2) that certain of these variants appear to be associated solely with ticks or with animals. Based on these observations, we now seek to determine experimentallywhether certain variants are more likely to be inherited by ticks, remain stable within the environment, or cause pulmonary pathology. The specific aims, therefore, are to: 1. Determine whether variants differ in their capacity to be transmitted by ticks, including maintenance by inheritance. We will clone strains from the multiple loci variable number tandem repeat analysis (MLVA)-defined genotypes, and measure the vector competence of various ticks for such clones. 2. Determine whether variants differ in their capacity to stably persist in the environment, including resistance to dessication, survival in water, and colonisation of freeliving or parasitic cyst-forming protozoa. We will measure the viability and survival of each genotype under simulated environmental stresses in vitro. 3. Determine whether variants differ in their infectivity to and virulence within rodents, including capacity to induce pulmonary pathology or hematogenously disseminate. Rats and mice will be infected by intratracheal instillation, as well as parenteral delivery, and tissues examined by histopathology,immunohistochemistry, PCR, cultivation, and cytokine mRNA expression. Taken together, these observations will provide a basis for understanding how the agent of tularemia is perpetuated on Martha's Vineyard, and why pneumonic human disease is prevalent there.

Francisella tularensis是Tularemia的病因，一种急性发热感染，具有可变的表现和 结果。尽管据说该特工是通过涉及壁虱和啮齿动物或兔子的周期来维持的 巨大的感染力和推定环境稳定性表明了持续的其他模式。我们的长期目标是 确定暴发爆发的近端决定因素，尤其是如何维持代理 在Epizootics之间。具体假设是多种传输模式由A促进 遗传变体的跨化变量结构在enzootic Focus中；某些变体可能会更好地适应 与环境水库相对的壁虱。我们将假设基于我们正在进行的肺炎的研究 玛莎葡萄园爆发的Tularemia爆发，我们发现（1）11 F. tularensis变体在我们的 岛研究地点； （2）某些这些变体似乎仅与壁虱或动物相关。 基于这些观察结果，我们现在试图在实验上确定某些变体更可能是 tick遗传，在环境中保持稳定或引起肺病理。因此，具体目标， 为：1。确定变体的滴答传输能力是否有所不同，包括维护 通过继承。我们将从多个基因座变量数字串联重复分析（MLVA）定义的克隆菌株 基因型，并测量此类克隆的各种壁虱的矢量能力。 2。确定是否变体 它们在环境中稳定稳定的能力有所不同，包括对腐败的抵抗力，在水中存活， 以及自由职业或寄生虫形成原生动物的定殖。我们将衡量每个的生存能力和生存 在模拟环境应力下的基因型体外。 3。确定变体的感染力是否有所不同 啮齿动物内的毒力和毒力，包括诱导肺病理或血源性的能力 传播。大鼠和小鼠将被气管内滴注以及肠胃外递送和组织感染 通过组织病理学，免疫组织化学，PCR，培养和细胞因子mRNA表达进行检查。拍摄 这些观察结果将共同理解tularemia剂的代理人在 玛莎（Martha）的葡萄园，以及为什么肺炎人类疾病在那里普遍存在。