Larsson Pär, Oyston Petra C F, Chain Patrick, Chu May C, Duffield Melanie, Fuxelius Hans-Henrik, Garcia Emilio, Hälltorp Greger, Johansson Daniel, Isherwood Karen E, Karp Peter D, Larsson Eva, Liu Ying, Michell Stephen, Prior Joann, Prior Richard, Malfatti Stephanie, Sjöstedt Anders, Svensson Kerstin, Thompson Nick, Vergez Lisa, Wagg Jonathan K, Wren Brendan W, Lindler Luther E, Andersson Siv G E, Forsman Mats, Titball Richard W
Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
Nat Genet. 2005 Feb;37(2):153-9. doi: 10.1038/ng1499. Epub 2005 Jan 9.
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.
土拉弗朗西斯菌是已知最具传染性的人类病原体之一。过去，前苏联和美国都曾开展过研制含有该细菌的武器的项目。我们报告了一株高毒力土拉弗朗西斯菌分离株（1,892,819 bp）的完整基因组序列。该序列揭示了以前未表征的编码IV型菌毛、一种表面多糖和铁获取系统的基因。几个与毒力相关的基因位于一个假定的致病岛中，该致病岛在基因组中是重复的。超过10%的假定编码序列包含插入缺失或替换突变，似乎正在退化。该基因组富含IS元件，包括IS630 Tc-1水手家族转座子，而这些元件在原核生物中并不常见。我们使用一种计算方法预测代谢途径，发现被破坏的途径比例出乎意料地高，这解释了该细菌苛刻的营养需求。生物合成途径的丧失表明土拉弗朗西斯菌在其自然生命周期中是一种严格依赖宿主的细菌。我们的结果对于我们理解高毒力人类病原体如何进化具有启示意义，并将加快对抗它们的策略。
