Development of genetic tools for Francisella tularensis

描述(申请人提供)：革兰氏阴性杆菌图拉氏亚种。图拉氏菌是图拉热症的病原体，被认为是一种潜在危险的生物武器。这是由于这种生物通过气雾剂途径具有极强的传染性，以及它所引起的人类疾病的严重性。这种细菌的挑剔性质，要求使用生物安全三级(BSL3)遏制来处理它，以及缺乏遗传工具，这些都阻碍了对这种有机体的研究。因此，与其他病原菌相比，图拉氏镰刀菌亚种所知甚少。图拉尔人的生理学、遗传学和发病机制。以前的研究使用的是图拉氏丝孢子虫亚种的减毒活疫苗株。Palaearctica，或罕见致病的F.tularensis亚种。诺维西达。这项建议的目的是开发基因工具来操纵毒力强、致病性的图拉氏丝孢子菌亚种。图拉尔人。然后，这些工具将被用于对图拉氏镰刀菌亚种的分析。图拉氏病的发病机制。此外，对生物体进行基因操作的能力将使减毒疫苗株的开发成为可能，这些疫苗株可以用于感染图拉氏丝虫的危险人群，无论是来自自然来源还是来自生物攻击。随着图拉氏镰刀菌亚种基因组测序的完成，方济氏菌遗传学的进一步发展是适时的。Tularens、Schu-4菌株基本完成。

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.