Perpetuation of Francisella tularensis

图拉氏弗朗西斯杆菌是图拉热症的病原体，图拉热症是一种急性发热性感染，具有不同的表现和 结果。虽然据说这种制剂在自然界中是通过扁虱、啮齿动物或兔子的循环维持的，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续模式。我们的长期目标是 确定暴发图拉热症风险的近端决定因素，特别是如何维持该制剂。 在动物流行性疾病之间。具体的假设是，多种传播模式由一种 疫源地内遗传变异的集合种群结构；某些变异可能更好地适应 扁虱，而不是环境水库。我们的假设是基于我们对正在进行的肺炎的研究。 在玛莎葡萄园岛暴发图拉热病，我们发现(1)11个图拉氏菌变种在我们的 岛屿研究地点；以及(2)这些变种中的某些似乎只与扁虱或动物有关。 基于这些观察，我们现在试图通过实验来确定某些变异是否更有可能是 由扁虱遗传，在环境中保持稳定，或引起肺部病理。因此，具体的目标是， 要做的是：1.确定扁虱传播的变异体的能力是否不同，包括维护 通过继承。我们将从多位点可变数目串联重复分析(MLVA)定义的克隆菌株 基因分型，并测量不同扁虱对这些克隆的媒介能力。2.确定变种是否 它们在环境中稳定生存的能力不同，包括抵抗干旱，在水中生存， 以及自由生活的或寄生的形成包囊的原生动物的定居。我们将衡量每一种生物的生存能力和生存能力 在体外模拟环境应激下的基因型。3.确定变异体的传染性是否不同 对啮齿动物的致病力和对啮齿动物的毒力，包括诱发肺部病变或血源性的能力 传播。大鼠和小鼠将通过气管内滴注以及非肠道给药和组织感染。 通过组织病理学、免疫组织化学、聚合酶链式反应、培养和细胞因子mRNA的表达进行检测。已被占用 综上所述，这些观察结果将为理解图拉热症的病原体如何持续存在提供基础。 玛莎葡萄园岛，以及为什么肺炎人类疾病在那里盛行。

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.