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.

土拉菌弗朗西斯菌是土拉菌病的病原体，土拉菌病是一种急性发热性感染，具有不同的表现和症状