Perpetuation of Francisella tularensis

土拉热弗朗西丝菌是土拉菌病的病原体，土拉菌病是一种急性发热性感染， 结果。虽然据说该药剂通过涉及蜱和啮齿动物或兔子的周期在自然界中维持，但其 强大的传染性和假定的环境稳定性使其他的永久化模式相形见绌。我们的长期目标是 确定土拉菌病爆发风险的近端决定因素，特别是如何维持制剂 动物流行病之间的联系具体的假设是，多种传播方式是由一种 地方病疫源地内遗传变异的集合种群结构;某些变异可能更适合 而不是环境中的寄生虫。我们的假设是基于对正在进行的肺炎的调查我们的假设是基于对正在进行的肺炎的调查 在玛莎葡萄园岛发生的兔热病中，我们发现：（1）11株F.土拉热变种在我们的 岛屿研究地点;（2）这些变异体中的某些似乎仅与蜱或动物有关。 基于这些观察结果，我们现在试图通过实验确定某些变体是否更有可能是 由蜱虫遗传，在环境中保持稳定，或引起肺部病变。因此，具体目标， 1.确定变异体通过蜱传播的能力是否不同，包括维持 通过继承。我们将从多位点可变数目串联重复序列分析（MLVA）中克隆菌株， 基因型，并测量各种蜱对这些克隆的载体能力。2.确定变体是否 不同的是它们在环境中稳定存在的能力，包括抗干燥性，水中存活， 以及自由生活或寄生的形成包囊的原生动物的定居。我们将衡量每一个人的生存能力和生存能力， 基因型在体外模拟环境胁迫下。3.确定变体的感染性是否不同 对啮齿类动物的毒性，包括诱导肺部病理或造血功能的能力， 传播。大鼠和小鼠将通过肠内滴注以及胃肠外递送和组织感染 通过组织病理学、免疫组化、PCR、细胞培养和细胞因子mRNA表达检测。采取 总之，这些观察结果将为理解土拉菌病的病原体是如何在 玛莎葡萄园岛，以及为什么人类肺炎在那里流行。

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.