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.

土拉热弗朗西斯菌是土拉热病的病原体，土拉热病是一种急性发热性感染，其表现各异， 结果。尽管据说这种物质在自然界中是通过蜱虫和啮齿动物或兔子的循环而维持的，但它的 巨大的传染性和假定的环境稳定性表明了其他的永久模式。我们的长期目标是 确定兔热病爆发风险的近端决定因素，特别是如何维持该药物 流行病之间。具体的假设是，多种传播模式是由 地方性动物病灶内遗传变异的集合种群结构；某些变体可能会更好地适应 蜱虫与环境水库相反。我们的假设基于对正在进行的肺炎的调查 玛莎葡萄园岛土拉热病爆发，其中我们发现 (1) 11 种土拉热土拉菌变种在我们的 岛屿研究地点； (2) 其中某些变体似乎仅与蜱或动物有关。 基于这些观察，我们现在试图通过实验确定某些变体是否更有可能被 由蜱遗传，在环境中保持稳定，或引起肺部病变。因此，具体目标 目的是： 1. 确定变体通过蜱传播的能力是否不同，包括维持能力 通过继承。我们将从多基因座可变数量串联重复分析 (MLVA) 定义的菌株中克隆菌株 基因型，并测量此类克隆的各种蜱的载体能力。 2. 判断是否有变体 它们在环境中稳定存在的能力不同，包括耐干燥、在水中生存、 以及自由生活或寄生的包囊形成原生动物的定殖。我们将衡量每个人的生存能力和生存能力 体外模拟环境胁迫下的基因型。 3. 确定变体的传染性是否不同 对啮齿类动物的毒力，包括诱发肺部病变或血源性病变的能力 传播。大鼠和小鼠会通过气管内滴注、肠胃外给药和组织感染 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。采取 总之，这些观察结果将为了解兔热病病原体如何在人体中长期存在提供基础。 玛莎葡萄园岛，以及为什么人类肺炎疾病在那里盛行。