Abstract

In the course of the three waves of the seventh cholera pandemic, the genome of the pathogen has undergone significant changes, which resulted in the emergence of new genetic variants with a high pathogenic and epidemic in the last decade. The aim of this study is to investigate the genomic diversity of the cholera agent and the prevalence of new genetic variants both in cholera-endemic regions and Russia, as well as to identify their phylogenetic relations. To search for new variants of the pathogen, bioinformatic analyses of the whole genome nucleotide sequences of 124 V. cholerae El Tor strains have been carried out. These strains were previously obtained by us or taken from the NCBI Gen Bank and European Nucleotide Archive database. Phylogenetic relations have been established based on SNP analysis for 115 different strains isolated in Asia, Africa, Russia, and Ukraine during three waves of the pandemic. Genomic analyses have been performed for 91 strains isolated in seven endemic countries between 2007 and 2019. According to the sets of mutant virulence and epidemicity genes localized in mobile genetic elements (CTXφ prophage, pathogenicity island VPI-1, and pandemic island VSP-II) and the core region, 74.7% of the studied strains are classified as new genetic variants of the pathogen. The genomic analyses of toxigenic strains from Russia and Ukraine (1970–2014) have revealed five groups that differ in mutations in key genes associated with virulence, epidemic potential, and drug resistance. According to the spectrum of mutant genes, 80.0% of the strains imported from endemic regions in recent years (2010–2014) have been recognized as new variants. According to the analysis of phylogenetic relations based on SNP typing of 115 strains, the new variants from Russia and Ukraine are phylogenetically similar to those circulating in Africa and Asia over the past decade. The results obtained are of interest for understanding the molecular mechanisms and dynamics of changes in the most important genetic properties of this pathogen and can also be used to develop methods for gene diagnostics of new variants of the pathogen.

中文翻译：

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霍乱病原体的新遗传变异及其在流行国家和俄罗斯的分布

摘要

在第七次霍乱大流行的三波过程中，病原体基因组发生了显着变化，导致近十年来出现了具有高致病性和流行性的新遗传变异体。本研究的目的是调查霍乱病原体的基因组多样性和新遗传变异在霍乱流行地区和俄罗斯的流行情况，并确定它们的系统发育关系。为了寻找病原体的新变种，对 124 个霍乱弧菌的全基因组核苷酸序列进行生物信息学分析El Tor菌株已经进行。这些菌株以前由我们获得或取自 NCBI Gen Bank 和 European Nucleotide Archive 数据库。基于对在三波大流行期间在亚洲、非洲、俄罗斯和乌克兰分离的 115 种不同毒株的 SNP 分析，建立了系统发育关系。对 2007 年至 2019 年间在 7 个流行国家分离的 91 株菌株进行了基因组分析。根据定位在移动遗传元件（CTXφ 原噬菌体、致病岛 VPI-1 和大流行岛 VSP-II）中的突变毒力和流行基因组。和核心区域，74.7%的研究菌株被归类为病原体的新遗传变异。对来自俄罗斯和乌克兰（1970-2014 年）的产毒菌株的基因组分析揭示了五组在与毒力、流行潜力和耐药性相关的关键基因突变方面存在差异。从突变基因谱来看，近年（2010-2014年）从流行地区输入的菌株中，80.0%被确认为新变种。根据基于115株SNP分型的系统发育关系分析，来自俄罗斯和乌克兰的新变种在系统发育上与过去十年在非洲和亚洲流行的变种相似。获得的结果对于了解该病原体最重要遗传特性的分子机制和变化动力学很有意义，也可用于开发该病原体新变种的基因诊断方法。