title: Genetic variations of live attenuated plague vaccine strains (Yersinia pestis EV76 lineage) during laboratory passages in different countries.
abstract: 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.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russia.
authors.forename: Andrey P
authors.initials: AP
authors.lastname: Anisimov
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Minoarisoa
authors.initials: M
authors.lastname: Rajerison
authors.affiliation: Yersinia Research Unit, National Reference Laboratory, Institut Pasteur, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Carniel
authors.affiliation: Environmental Research Institute, University College Cork, Cork, Ireland, United Kingdom; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: ruifuyang@gmail.com.
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Environmental Research Institute, University College Cork, Cork, Ireland, United Kingdom. Electronic address: songyajun88@gmail.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Song
mesh_terms: D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D005843:Geography; D006801:Humans; D054643:INDEL Mutation; D009154:Mutation; D010802:Phylogeny; D058974:Phylogeography; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D014613:Vaccines, Attenuated; D015010:Yersinia pestis / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D010931:Plague Vaccine; D014613:Vaccines, Attenuated
keywords: EV76; Genetic variation; Live vaccine; Yersinia pestis