Abstract

The genomic instability of the cholera agent leads to the emergence of its new variants with altered epidemically significant features. This makes investigation of the dynamics in pathogenicity gene structure and cholera vibro persistence changes over extended periods of time important. Bioinformatic analysis of whole genome nucleotide sequences was carried out in 44 toxigenic and nontoxigenic Vibrio cholerae O1 strains, biovar El Tor, isolated before the onset and in different periods of the current pandemic, with 29 of them being found in Russia. SNP-typing was performed using Bayesian evolutionary analysis with BEAST v2.5.1. Based on SNP-analysis, it was demonstrated that the importation of epidemically hazardous strains into the territory of Russia (1970–2014) overlapped with three different waves of the global spread of cholera. Comparison of the nucleotide sequences of genomic regions determining their virulence and ability to spread epidemically confirmed that there were multilayered rapid changes in cholera vibrios during evolution. For the first time ever, it has been established that the genomes of pathogenicity islands, VPI-1 and VPI-2, of prepandemic strains contained different mutations, which distinguish them from the genome of pandemic strains. At the same time, we have revealed conservation of nucleotide sequences of all the studied persistence genes from VPI-2 and EPI of pandemic isolates. On the contrary, the modern nontoxigenic strains ctxA^–tcpA^– show considerable variability of persistence genes that are parts of the structure of these mobile elements. New data on the structure of regions of the V. cholerae genome associated with persistence can be used to differentiate V. cholerae of different epidemic significance.

中文翻译：

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埃尔托霍乱弧菌基因组在当前大流行发病前和不同时期分离的变异性

摘要

霍乱病原体的基因组不稳定性导致其具有改变的流行显着特征的新变体的出现。这使得研究致病性基因结构的动态和长时间内霍乱振动持续性变化变得很重要。对 44 种产毒和非产毒霍乱弧菌进行全基因组核苷酸序列的生物信息学分析O1 菌株，生物型 El Tor，在当前大流行的发病前和不同时期分离，其中 29 种在俄罗斯被发现。SNP 分型是使用贝叶斯进化分析和 BEAST v2.5.1 进行的。根据 SNP 分析，证明具有流行病危险的菌株输入俄罗斯境内（1970-2014 年）与霍乱全球传播的三个不同浪潮重叠。确定其毒力和流行性传播能力的基因组区域的核苷酸序列的比较证实，霍乱弧菌在进化过程中存在多层快速变化。有史以来第一次确定了大流行前毒株的致病岛 VPI-1 和 VPI-2 的基因组包含不同的突变，这将它们与大流行毒株的基因组区分开来。同时，我们揭示了来自大流行分离株的 VPI-2 和 EPI 的所有研究持久性基因的核苷酸序列的保守性。相反，现代无毒菌株ctxA ^– tcpA ^–显示持久性基因的相当大的可变性，这些基因是这些移动元素结构的一部分。与持久性相关的霍乱弧菌基因组区域结构的新数据可用于区分具有不同流行意义的霍乱弧菌。