Development of genetic tools for Francisella tularensis

描述（由申请人提供）：革兰氏阴性菌土拉菌弗朗西斯菌亚种。土拉菌是土拉菌病的病原体，被认为是一种潜在的危险生物武器。这是由于这种生物通过气溶胶途径具有极强的传染性，以及它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）容器来处理它，以及遗传工具的缺乏阻碍了对这种生物的研究。因此，与其他病原体相比，对土拉菌亚种知之甚少。土拉菌的生理学、遗传学和发病机制。以前的研究使用了来自土拉菌亚种的减毒活疫苗（LVS）。古北极菌，或很少致病的土拉菌亚种。novicida。本提案的目的是开发遗传工具，以操纵毒力，致病性土拉菌亚种。土拉杆菌内。这些工具随后将用于土拉菌亚种的分析。土拉杆菌内发病。此外，基因操纵生物体的能力将允许开发减毒疫苗株，可用于面临土拉菌感染风险的人群，无论是从自然来源还是从生物攻击。随着土拉菌亚种基因组的测序，弗朗西斯菌遗传学的进一步发展是及时的。土拉菌，菌株Schu 4几乎完成了。

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.