PDF(Pubmed)
Abstract：
Francisella tularensis, the causative agent of tularemia, is divided into three subspecies. Two of these, subspecies holarctica and tularensis, are highly pathogenic to humans and consequently relatively well studied. The third subspecies, mediasiatica, is rarely isolated and remains poorly studied. It is distributed in the sparsely populated regions of Central Asia and Siberia. Curently this subspecies is not known to have been responsible for human infections in spite of its high virulence in laboratory animals. Subspecies mediasiatica is currently divided into three subgroups-MI, present in Central Asia, MII, present in southern Siberia, and MIII represented by a unique strain, 60(B)57, isolated in Uzbekistan in 1960. We describe here the unexpected observation that MIII strain 60(B)57 is avirulent and immunogenic. We observed that infection with this strain protected mice from challenge 21 days later with a virulent subsp. mediasiatica strain. With an increase of this interval, the protection for mice was significantly reduced. In contrast, guinea pigs were protected from challenge with strains of the subspecies holarctica and mediasiatica (but not subsp. tularensis) 90 days after infection with 60(B)57. We performed genome assembly based on whole genome sequencing data obtained using the Nanopore MinION for strain 60(B)57 and two subsp. mediasiatica strains representing the Central Asian MI and Siberian MII phylogenetic subgroups. The prmA gene is truncated due to a nonsense mutation in strain 60(B)57. The deletion of gene prmA has previously been shown to induce a loss of virulence in Francisella novicida the closest model organism suggesting that the observed mutation might the cause of the avirulence of strain 60(B)57.
摘要：
图拉西斯,Tularemia的病原体,分为三个亚种。其中两个，南极亚种和图拉西斯，对人类有很高的致病性，因此进行了相对较好的研究。第三个亚种,mediasiatica,很少被孤立，并且研究不足。它分布在中亚和西伯利亚人口稀少的地区。尽管该亚种在实验动物中具有很高的毒力，但目前尚不知道该亚种是人类感染的原因。媒介亚种目前分为三个亚组-MI，目前在中亚，MII,目前在西伯利亚南部，MIII由一种独特的菌株代表，60（B）57，1960年在乌兹别克斯坦隔离。我们在此描述了MIII菌株60(B)57是无毒和免疫原性的意外观察。我们观察到，该菌株的感染可保护小鼠在21天后免受毒力亚种的攻击。mediasiatica菌株。随着这个间隔的增加，对小鼠的保护作用显著降低。相比之下,保护豚鼠免受holarctica和mediasiatica亚种菌株的攻击（但不是亚种。tularensis）感染后90天（B）57。我们基于使用NanoporeMinION对菌株60（B）57和两个亚种获得的全基因组测序数据进行了基因组组装。代表中亚MI和西伯利亚MII系统发育亚组的mediasiatica菌株。由于菌株60(B)57中的无义突变,prmA基因被截短。先前已显示基因prmA的缺失会在最接近的模型生物中诱导毒力丧失，这表明观察到的突变可能是菌株60（B）57的无毒力的原因。
