Cui Yujun, Yang Xianwei, Xiao Xiao, Anisimov Andrey P, Li Dongfang, Yan Yanfeng, Zhou Dongsheng, Rajerison Minoarisoa, Carniel Elisabeth, Achtman Mark, Yang Ruifu, Song Yajun
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russia.
Infect Genet Evol. 2014 Aug;26:172-9. doi: 10.1016/j.meegid.2014.05.023. Epub 2014 Jun 4.
Plague, one of the most devastating infectious diseases in human history, is caused by the bacterial species Yersinia pestis. A live attenuated Y. pestis strain (EV76) has been widely used as a plague vaccine in various countries around the world. Here we compared the whole genome sequence of an EV76 strain used in China (EV76-CN) with the genomes of Y. pestis wild isolates to identify genetic variations specific to the EV76 lineage. We identified 6 SNPs and 6 Indels (insertions and deletions) differentiating EV76-CN from its counterparts. Then, we screened these polymorphic sites in 28 other strains of EV76 lineage that were stored in different countries. Based on the profiles of SNPs and Indels, we reconstructed the parsimonious dissemination history of EV76 lineage. This analysis revealed that there have been at least three independent imports of EV76 strains into China. Additionally, we observed that the pyrE gene is a mutation hotspot in EV76 lineages. The fine comparison results based on whole genome sequence in this study provide better understanding of the effects of laboratory passages on the accumulation of genetic polymorphisms in plague vaccine strains. These variations identified here will also be helpful in discriminating different EV76 derivatives.
鼠疫是人类历史上最具毁灭性的传染病之一，由鼠疫耶尔森菌引起。一种减毒活鼠疫耶尔森菌菌株（EV76）在世界各国被广泛用作鼠疫疫苗。在此，我们将中国使用的一株EV76菌株（EV76-CN）的全基因组序列与鼠疫耶尔森菌野生分离株的基因组进行比较，以鉴定EV76谱系特有的遗传变异。我们鉴定出6个单核苷酸多态性（SNP）和6个插入缺失（Indel，插入和缺失），这些变异使EV76-CN与其对应菌株区分开来。然后，我们在保存在不同国家的其他28株EV76谱系菌株中筛选了这些多态性位点。基于SNP和Indel的图谱，我们重建了EV76谱系的简约传播历史。该分析表明，至少有三次独立的EV76菌株传入中国。此外，我们观察到pyrE基因是EV76谱系中的一个突变热点。本研究基于全基因组序列的精细比较结果，有助于更好地理解实验室传代对鼠疫疫苗株遗传多态性积累的影响。这里鉴定出的这些变异也将有助于区分不同的EV76衍生物。
