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首页> 外文期刊>Infection and immunity >Potential Source of Francisella tularensis Live Vaccine Strain Attenuation Determined by Genome Comparison
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Potential Source of Francisella tularensis Live Vaccine Strain Attenuation Determined by Genome Comparison

机译：基因组比较确定土拉弗朗西斯菌活疫苗株衰减的潜在来源

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Francisella tularensis is a bacterial pathogen that causes the zoonotic disease tularemia and is important to biodefense. Currently, the only vaccine known to confer protection against tularemia is a specific live vaccine strain (designated LVS) derived from a virulent isolate of Francisella tularensis subsp. holarctica. The origin and source of attenuation of this strain are not known. To assist with the design of a defined live vaccine strain, we sought to determine the genetic basis of the attenuation of LVS. This analysis relied primarily on the comparison between the genome of LVS and Francisella tularensis holarctica strain FSC200, which differ by only 0.08% of their nucleotide sequences. Under the assumption that the attenuation was due to a loss of function(s), only coding regions were examined in this comparison. To complement this analysis, the coding regions of two slightly more distantly related Francisella tularensis strains were also compared against the LVS coding regions. Thirty-five genes show unique sequence variations predicted to alter the protein sequence in LVS compared to the other Francisella tularensis strains. Due to these polymorphisms, the functions of 15 of these genes are very likely lost or impaired. Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine.
机译：图拉弗朗西斯菌是一种细菌性病原体，可导致人畜共患病，并对生物防御具有重要意义。目前，已知唯一可提供抗图拉血病保护的疫苗是一种特异的活疫苗株（命名为LVS），该菌株衍生自强毒的杜拉弗朗西斯菌变种亚种。 holarctica 。该应变的衰减的起源和来源尚不清楚。为了帮助设计确定的活疫苗株，我们试图确定LVS减毒的遗传基础。该分析主要基于LVS基因组与图拉弗朗西斯菌larcella 菌株FSC200的基因组比较，它们的核苷酸序列仅相差0.08％。假设衰减是由于功能损失造成的，则在此比较中仅检查了编码区域。为了补充这一分析，还比较了两个距离稍远的 Tulcisella tularensis 菌株的编码区和LVS编码区。与其他 Francisella tularensis 菌株相比，有35个基因显示出独特的序列变异，预计会改变LVS中的蛋白质序列。由于这些多态性，这些基因中的15个的功能极有可能丧失或受损。这些基因中的七个被证明在更强的选择性约束下，这表明它们最有可能是LVS减毒的来源，并且可用于新定义的疫苗。

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