The complete genome sequence of Francisella tularensis, the causative agent of tularemia
The complete genome sequence of Francisella tularensis, the causative agent of tularemia
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DOI：
10.1038/ng1499
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发表时间：
2005-02-01
期刊：
影响因子：
30.8
通讯作者：
Titball, RW
中科院分区：
文献类型：
--
作者：
Larsson, P;Oyston, PCF;Titball, RW
土拉热弗朗西斯菌是已知的最具传染性的人类病原体之一。过去，前苏联和美国都有开发含有这种细菌的武器的计划。我们报道了一株高毒力F. tularensis（1，892，819 bp）。该序列揭示了以前未知的基因编码IV型皮利，表面多糖和铁的收购系统。几个毒力相关基因位于一个假定的毒力岛上，该毒力岛在基因组中是重复的。超过10%的推定编码序列含有插入-缺失或取代突变，似乎正在恶化。基因组富含IS元件，包括IS 630 Tc-1 mariner家族转座子，这在原核生物中是不期望的。我们使用了一种计算方法来预测代谢途径，并发现了一个出乎意料的高比例的中断途径，解释了细菌的挑剔的营养需求。生物合成途径的丧失表明F.土拉菌在其自然生命周期中是专性宿主依赖性细菌。我们的研究结果对我们理解高毒性人类病原体如何进化具有重要意义，并将加快对抗它们的战略。
Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892, 819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.