D. A. Rybal’chenko, Yu. V. Lozovsky, Ya. M. Krasnov, E. Yu. Shchelkanova, N. I. Smirnova
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引用次数: 0
Abstract
A comparative analysis of the genome of nontoxigenic and toxigenic V. cholerae O1 El Tor strains identified in Russia in 2023 and their phylogenetic analysis were performed. We used V. cholerae O1 El Tor strains isolated from patients and from an aquatic environment in 2023 in Russia. Analysis of their sequenced genomes was performed with the UGENE v.45.1 and Bandage v.0.8.1 software. To carry out SNP analysis, nucleotide sequences of the complete genomes of 63 V. cholerae El Tor strains obtained by us (41 strains) and from the NCBI GenBank database (22 strains) were used. Conventional methods were used to assess the phenotypic characteristics of strains (susceptibility to antibiotics, hemolysin and protease production, and motility). Analysis of the sequenced complete genomes of V. cholerae El Tor strains isolated from patients and from an aquatic environment in 2023 in Russia showed their genetic diversity. Toxigenic strains belonged to different types of genovariants with different mutations in the genome of transposable elements, as well as in core genes associated with pathogenicity, the ability to spread epidemically, and drug resistance. The clinical strain M3208 had a full set of altered virulence genes (ctxB7, tcpACIRS101, and rtxA4) and epidemicity (VSP-IIΔ) characteristic of new variants with high pathogenic potential that were widespread during the third wave of the pandemic. In addition, the resulting mutations led to the emergence of resistance to nalidixic acid (Nalr) and the loss of resistance to polymyxin B (Pols). The second toxigenic strain M3210, isolated from river water, differed from the strain M3208 in the composition of mutant genes, since it had only one altered gene (ctxB). The genotype of this strain (ctxB1tcpAEltorrtxA1VSP-II) was identical to that of previously appearing genovariants with a lower level of virulence from the second wave of the pandemic, which persisted only in several endemic regions. By contrast, the nontoxigenic isolate M3209 from a patient with acute enteric disease was devoid of not only the CTXφ prophage but also other transposable elements carrying key pathogenicity and epidemic genes. Only the deleted VPI-2 pandemic island was present in its genome. This strain was shown to produce additional pathogenicity factors (hemolysin, soluble hemagglutinin/protease, and motility), which could lead to the development of gastroenteritis in infected individuals. The genomic diversity of V. cholerae El Tor strains introduced into Russia in 2023 was revealed. Toxigenic strains were shown to be different genovariants with altered epidemically important properties. Among them, the clinical toxigenic strain M3208 was classified as a new genovariant with high pathogenic potential based on its mutant genes.
摘要 对2023年在俄罗斯发现的非致毒霍乱弧菌O1 El Tor菌株和致毒霍乱弧菌O1 El Tor菌株的基因组进行了比较分析和系统发育分析。我们使用了 2023 年在俄罗斯从病人和水生环境中分离出的霍乱弧菌 O1 El Tor 菌株。我们使用 UGENE v.45.1 和 Bandage v.0.8.1 软件对它们的基因组测序进行了分析。为了进行 SNP 分析，使用了我们获得的 63 株霍乱弧菌 El Tor 株系（41 株）和 NCBI GenBank 数据库（22 株）的完整基因组核苷酸序列。采用常规方法评估菌株的表型特征（对抗生素的敏感性、溶血素和蛋白酶的产生以及运动能力）。对 2023 年从患者体内和俄罗斯水生环境中分离出的霍乱弧菌 El Tor 株系的完整基因组测序分析表明了它们的遗传多样性。致毒菌株属于不同类型的基因变异体，其基因组中的转座元件以及与致病性、流行传播能力和耐药性相关的核心基因发生了不同的突变。临床菌株 M3208 的致病基因（ctxB7、tcpACIRS101 和 rtxA4）和流行性（VSP-IIΔ）发生了全套改变，具有在第三波大流行期间广泛传播的高致病性新变异株的特征。此外，由此产生的变异导致了对萘啶酸（Nalr）的抗药性和对多粘菌素 B（Pols）抗药性的丧失。从河水中分离出的第二株致毒菌株 M3210 与菌株 M3208 的突变基因组成不同，因为它只有一个改变的基因（ctxB）。该菌株的基因型（ctxB1tcpAEltorrtxA1VSP-II）与之前在第二波大流行中出现的毒力较低的基因变异株的基因型相同，这些基因变异株仅在几个流行地区持续存在。相比之下，从一名急性肠道疾病患者身上分离出的无毒分离株 M3209 不仅没有 CTXφ 原体，也没有携带关键致病性和流行病基因的其他转座元件。其基因组中只有被删除的 VPI-2 大流行岛。研究表明，该菌株能产生额外的致病因子（溶血素、可溶性血凝素/蛋白酶和运动性），这可能导致受感染者患上肠胃炎。研究揭示了 2023 年引入俄罗斯的霍乱弧菌 El Tor 株系的基因组多样性。研究表明，致毒菌株是不同的基因变异体，其重要的流行病特性发生了改变。其中，临床致毒菌株M3208根据其突变基因被归类为具有高致病性的新基因变异株。
期刊介绍：
Molecular Genetics, Microbiology and Virology is a journal that covers most topical theoretical and applied problems of molecular genetics of pro- and eukaryotic organisms, molecular microbiology and molecular virology. An important part the journal assigns to investigations of the genetic apparatus of microorganisms, searching for forms of genetic exchange, genetic mapping of pathogenic causative agents, to ascertainment of the structure and functions of extrachromosomal factors of heredity and migratory genetic elements, to theoretical studies into the mechanisms of genetic regulation. The journal publishes results of research on molecular and genetic bases of an eukaryotic cell, functioning of chromosomes and chromatin, nature of genetic changes in malignization and a set of hereditary diseases. On the pages of the journal there is covered the formulation of molecular bases of virology including issues of integration of viral and cellular genomes, and issues of persistence. The journal plans to put materials on genetic engineering, envisaging synthesis and isolation of genes from natural reservoirs, creation of plasmid- and virus-based vector, production of recombinant DNA molecules, the creation of Gene Banks for Microbes, animals, and human; and also on biotechnological production of hormones, components of antiviral vaccines, diagnostic and therapeutic preparations.
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