公开(公告)号：US20090202586A1

公开(公告)日：2009-08-13

申请号：US12016567

申请日：2008-01-18

申请人： Burt Anderson ,  Wendy Sammons ,  Jean Citron ,  Chandra Shekhar Bakshi ,  Dennis Metzger

发明人： Burt Anderson ,  Wendy Sammons ,  Jean Citron ,  Chandra Shekhar Bakshi ,  Dennis Metzger

IPC分类号： A61K39/02 ,  C12N1/21 ,  C12N15/11

CPC分类号： A61K39/0208 ,  A61K2039/522 ,  Y02A50/405

摘要： A scan of F. tularensis genome for homology to a regulatory protein that controls virulence identified gene FTL0552. A knock out mutation in FTL0552 was created using reverse transcriptase PCR and the construct inserted into F. tularensis. This mutant was defective for survival in macrophages and found avirulent in in vivo testing, where the mutant exhibited reduced levels of pro-inflammatory cytokine production, reduced evidence of histopathology in affected tissues, reduced systemic infection, and rapid clearance of the bacterium. In vivo challenge studies with the FTL0552 mutant using the virulent F. tularensis subsp. tularensis SchuS4 strain show an immune response is induced, and protection afforded, after preexposure to the FTL0552 mutant. Microarray studies revealed 148 genes regulated by FTL0552, including genes located within the FPI that are essential for intracellular survival.

摘要翻译： 与控制毒力鉴定基因FTL0552的调节蛋白的同源性的土拉曼氏弧菌基因组的扫描。 使用逆转录酶PCR产生FTL0552中的敲除突变，并将该构建体插入到土拉氏木霉中。 该突变体在巨噬细胞中存活有缺陷并且在体内测试中无毒性，其中突变体表现出减少的促炎细胞因子产生水平，减少受影响组织中组织病理学的证据，减少的全身感染和细菌的快速清除。 使用FTL0552突变体的体内攻击研究，使用强毒的土拉氏木霉亚种 土拉氏SchuS4菌株显示免疫反应被诱导，并且在暴露于FTL0552突变体后得到保护。 微阵列研究揭示了由FTL0552调控的148个基因，包括位于FPI内的基因对于细胞内存活是必需的。