Francisella tularensis Pathogenesis

土拉弗朗西斯菌发病机制

• 批准号: 8513890
• 负责人: Thomas H KAWULA
• 金额: $ 34.05万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-16 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513890
• 关键词: Affect; Animals; Bacteria; Binding Proteins; Biochemical; Bioinformatics; Biological; Biology; Cell membrane; Cells; Characteristics; Containment; Cytoplasm; Dendrites; Development; Environment; Epithelial Cells; Escape Mutant; Francisella; Francisella tularensis; Frequencies; Genes; Genetic; Goals; Gram-Negative Bacterial Infections; Growth; Human; Immune response; Immunoprecipitation; Immunosuppression; Infection; Inflammatory; Invaded; Laboratories; Lung diseases; Maps; Membrane Proteins; Methods; Modeling; Mutagenesis; Mutation; Open Reading Frames; Organism; Orthologous Gene; Pathogenesis; Phagosomes; Phenotype; Post-Translational Protein Processing; Property; Proteins; Regulation; Research; Role; Sequence Homology; Site; Site-Directed Mutagenesis; Structure; Testing; Time; Transmembrane Domain; Virulence; Virulent; Yeasts; cell type; cytokine; genetic analysis; insight; macrophage; mutant; pathogen; periplasm; public health relevance; resilience; tool; yeast two hybrid system

DESCRIPTION (provided by applicant): Francisella tularensis is an extremely virulent Gram negative, facultative intracellular bacterial pathogen capable of causing rapidly progressing lethal infections in literally hundreds of diverse animal species, including humans. Although the general properties of Francisella virulence and pathogenesis are understood, the function of any one Francisella protein not assured by sequence homology remains essentially unknown. This situation is due, in part, to the fact that most open reading frames in Francisella have no known orthologs. Our goal is to uncover and experimentally determine unknown mechanisms and properties that contribute to virulence and pathogenesis. Herein we propose to define the function of RipA, which is a cytoplasmic membrane protein that is conserved among Francisella and is required for adaptation to the host cell environment. This goal will be accomplished through genetic and phenotypic analysis of ripA mutants and extragenic suppressors of ripA mutant phenotypes, identification of RipA - binding proteins, biophysical studies on RipA topology and structure, and regulation of ripA expression.

描述（由申请人提供）：土拉菌弗朗西斯菌是一种极毒的革兰氏阴性，兼性细胞内细菌病原体，能够在包括人类在内的数百种不同动物物种中引起快速进展的致命感染。虽然我们已经了解了Francisella的毒力和发病机制的一般特性，但任何一种Francisella蛋白的功能，如果不通过序列同源性来确定，基本上仍然是未知的。这种情况部分是由于Francisella的大多数开放阅读框架没有已知的同源词。我们的目标是揭示和实验确定未知的机制和性质，有助于毒力和发病机制。RipA是一种细胞质膜蛋白，在Francisella中是保守的，是适应宿主细胞环境所必需的。这一目标将通过对ripA突变体的遗传和表型分析、ripA突变体表型的外基因抑制因子、ripA结合蛋白的鉴定、ripA拓扑和结构的生物物理研究以及ripA表达的调控来实现。