Development of genetic tools for Francisella tularensis

描述（由申请人提供）：革兰氏阴性菌土拉热弗朗西斯菌亚种（Francisella tularensis subsp.）土拉热是土拉菌病的病原体，被认为是一种潜在危险的生物武器。 这是由于微生物通过气溶胶途径的极端传染性及其引起的人类疾病的严重性。 这种细菌的挑剔性、使用生物安全三级（BSL 3）控制的要求以及遗传工具的缺乏阻碍了对这种生物体的研究。 因此，与其他病原体相比，对F.土拉热亚种土拉热生理学、遗传学和发病机理。 以前的研究使用了来自F.土拉热亚种palaearctica或罕见致病性F.土拉热亚种novicida。 该建议的目的是开发用于操纵有毒、致病性F.土拉热亚种土拉热。 这些工具将被用于分析F。土拉热亚种土拉热病发病机制 此外，遗传操作该生物体的能力将允许开发减毒疫苗株，该减毒疫苗株可用于有感染F.土拉热感染，无论是从自然来源或从生物攻击。 随着弗朗西斯菌基因组测序的完成，弗朗西斯菌遗传学的进一步发展是及时的。土拉热亚种土拉热菌Schu 4株几乎完全。

DESCRIPTION (provided by applicant): The Gram-negative bacterium Francisella tularensis subsp. tularensis, the causative agent of tularemia, is considered a potentially dangerous biological weapon. This is due to the organism's extreme infectivity via the aerosol route and the severity of the human disease it causes. The fastidious nature of the bacterium, the requirement that it be handled using biosafety level three (BSL3) containment, and the paucity of genetic tools have hindered research on this organism. Thus, compared to other pathogens, little is known about F. tularensis subsp. tularensis physiology, genetics, and pathogenesis. Previous studies have used the attenuated live vaccine strain (LVS) derived from F. tularensis subsp. palaearctica, or the rarely pathogenic F. tularensis subsp. novicida. The aim of this proposal is to develop genetic tools for the manipulation of virulent, pathogenic F. tularensis subsp. tularensis. These tools will then be used for the analysis of F. tularensis subsp. tularensis pathogenesis. Furthermore, the ability to genetically manipulate the organism will allow for the development of attenuated vaccine strains that could be administered to populations at risk from F. tularensis infection, either from natural sources or from a biological attack. The further development of Francisella genetics is timely, as the sequencing of the genome of the F. tularensis subsp. tularensis, strain Schu 4 is almost complete.