Molecular and genetic basis of pathogenesis in Francisella tularensis
Molecular and genetic basis of pathogenesis in Francisella tularensis
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DOI：
10.1196/annals.1409.010
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Klose, Karl E.
中科院分区：
文献类型：
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作者：
Barker, Jeffrey R.;Klose, Karl E.
土拉菌病发病的遗传机制尚不清楚。土拉菌能够在巨噬细胞内存活和复制，并且已经确定了一种毒力因子MgIA对这种能力至关重要。MglA调节细胞内生长所需基因的转录，包括位于Francisella致病岛（FPI）内的基因。FPI基因是巨噬细胞生长和毒力所必需的，似乎编码了一个蛋白质分泌系统，但单个FPI蛋白的确切功能仍有待确定。最近发现了毒力所需的其他调节因子，以及通过转座子突变体筛选鉴定的一些毒力基因。表面成分的作用，包括脂多糖，毛，和胶囊，土拉菌的毒力也开始被阐明。毒力基因的鉴定使研究确定的减毒突变体作为兔热病活疫苗株成为可能。随着土拉菌毒力基因库的新成分的发现，我们将更好地了解这种细菌如何与宿主相互作用并逃避免疫功能，这将促进土拉菌病治疗和预防措施的发展。
The genetic means of pathogenesis of Francisella tularensis are poorly understood. F. tularensis is able to survive and replicate within macrophages, and a virulence factor, MgIA, has been identified that is essential for this ability. MglA regulates the transcription of genes necessary for intracellular growth, including those located within the Francisella Pathogenicity Island (FPI). The FPI genes are required for intramacrophage growth and virulence, and appear to encode a protein secretion system, but the exact function of individual FPI proteins remains to be determined. Additional regulatory factors required for virulence have recently been discovered, as well a number of virulence genes identified through transposon mutant screens. The role of surface components, including LPS, pili, and capsule, in F. tularensis virulence is also beginning to be illuminated. The identification of virulence genes has enabled the study of defined attenuated mutants as live vaccine strains against tularemia. As new components of the F tularensis virulence gene repertoire are discovered, we will achieve a better understanding of how this bacterium interacts with the host and evades immune function, which will facilitate the development of therapeutic and preventive measures against tularemia.