Early ancient sublineages of Mycobacterium tuberculosis Beijing genotype: unexpected clues from phylogenomics of the pathogen and human history

Mokrousov, Igor; Vyazovaya, Anna; Pasechnik, Oksana; Gerasimova, Alena; Дымова, М. А.; Chernyaeva, Ekaterina; Татаринцева, М. П.; Стасенко, В. Л.

doi:10.1016/j.cmi.2018.11.024

Cited by 19 publications

(22 citation statements)

References 24 publications

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“…This study was undertaken to assess the biological properties of two M. tuberculosis strain clusters emerging in the Asian part of Russia. These strains have recently attracted attention due to their unexpectedly strong association with MDR/XDR and local population increase [ 11 , 12 , 15 ]. We studied particular features of the in vitro growth of these strains and used a model of pulmonary infection of C57BL/6 mice to assess their virulence.…”

Section: Discussionmentioning

confidence: 99%

“…It belongs to the Beijing 14717-15-cluster that accounts for non-negligible 16% of the total M. tuberculosis population in Buryatia, Far East. However only very rare isolates of this cluster were described in other Russian regions – 11/423 (2.6%) in Omsk and single isolate per region in Irkutsk, Sakhalin, Kemerovo – all are in the Asian part of Russia ([ 11 ] and references therein) (Figure S2). A closer look at human migration data to/from Buryatia reveals that the region has lost 402700 people since the beginning of the 1990s (while its population is 985900) as a result of the permanent economic migration outflow to the more developed regions [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…VNTR typing and spoligotyping and detection of other molecular markers were performed as described previously [ 11 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…One of the clusters, Mlva 1071-32 was most prevalent (7%) in Omsk, Siberia, and sporadically described in different parts of Russia since the mid-1990s. The second cluster Mlva 14717-15 was found only in Asian Russia where it showed some gradient from 2.6% in Omsk [ 11 ] to 16% in Buryatia, Far East [ 12 ] (Figure S2).…”

Section: Introductionmentioning

confidence: 99%

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Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

Vinogradova

Dogonadze

Заболотных

et al. 2021

Emerging Microbes & Infections

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Mycobacterium tuberculosis strains of the early ancient sublineage of the Beijing genotype are mostly drug susceptible and mainly circulate in East Asia. We have recently discovered two clusters of this sublineage emerging in the Asian part of Russia (VNTR-defined 1071-32 and 14717-15 types) and, to our surprise, both were strongly MDR/XDR-associated. Here, we evaluated their pathogenic features. The clinical isolates and reference laboratory strain H37Rv were investigated in the C57BL/6 mouse model to assess their virulence and lethality properties. The BACTEC MGIT 960 system was used to study the in vitro growth characteristics. In the murine model, strains 396 (14717-15-cluster, from Buryatia, Far East) and 6691 (1071-32-cluster, from Omsk, Siberia) demonstrated contrasting properties. The 396-infected group had significantly higher mortality, more weight loss, higher bacterial burden, and more severe lung pathology. Furthermore, compared to the previously published data on other Russian epidemic Beijing strains (B0/W148, CAO, Central Asian Russian), strain 396 demonstrated the highest mortality. Under the in vitro growth experiment, cluster 14717-15 isolates had significantly shorter lag-phase. To conclude, low-virulent MDR strain 6691 belongs to the Beijing 1071-32-cluster widespread across FSU countries but at low prevalence. This corresponds to common expectation that multiple drug resistance mutations reduce fitness and virulence. In contrast, highly lethal and hypervirulent MDR strain 396 represents an intriguing Beijing 14717-15 cluster predominant only in Buryatia, Far East (16%), sporadically found beyond it, but not forming clusters of transmission. Further in-depth study of this most virulent Russian Beijing cluster is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…VNTR typing and spoligotyping and detection of other molecular markers were performed as described previously [ 11 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

Vinogradova

Dogonadze

Заболотных

et al. 2021

Emerging Microbes & Infections

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“…Генотип разделяют на древние (предковые) и современные сублинии, при этом в России преобладают штаммы современной сублинии, прежде всего, следует отметить эпидемический кластер Beijing B0 [4,5]. При этом, для штаммов древней сублинии в Японии и Корее ранее были описаны различия в особенностях развития лекарственной устойчивости и степени кластеризации как прокси-маркера трансмиссивности [6][7][8] и недавно был выявлен резистентный кластер древней сублинии генотипа Beijing в Западной Сибири [9].…”

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Применение полногеномного анализа для определения молекулярных маркеров значимых генетических кластеров Mycobacterium tuberculosis в России

Mokrousov¹,

Chernyaeva²,

Vyazovaya³

et al. 2019

Nauchno-Prakticheskii Zhurnal «Patogenez»

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Актуальность. Туберкулёз относят к числу «вновь вернувшихся» заболеваний, получивших эпидемическое распространение во многих регионах мира. Фундаментальный интерес представляет понимание генетических основ адаптации возбудителя заболевания Mycobacterium tuberculosis к организму хозяина. Целью данного исследования было выявление молекулярных маркеров для значимых геновариантов M. tuberculosis в России на основе проведения полногеномного и биоинформационного анализа. Материалы и методы. Полногеномное секвенирование и филогенетический анализ были проведены для репрезентативной выборки штаммов M. tuberculosis Восточно-Азиатской линии (древние и современные сублинии генотипа Beijing) и Евро-Американской линии (штаммы генотипов LAM, T и S). Результаты. В результате филогенетического анализа геномных данных (4500 полиморфных нуклеотидных позиций), были выделены кластеры штаммов и определены их специфические однонуклеотидные полиморфизмы (ОНП, SNP). В частности, внутри сублинии LAM-RUS был выявлен эволюционно «молодой» кластер, включающий штаммы сполиготипов SIT252 и SIT266. Внутри штаммов семейства Beijing были выделены ветви современной (субтипы В0 и 94-32) и древней сублиний. Среди выявленных кластер-специфических однонуклеотидных полиморфизмов для групп внутри семейств Beijing и LAM наиболее широко были представлены категории генов «процессы, связанные с клеткой и клеточной стенкой» и «промежуточный метаболизм и дыхание». Вариации в генах категории «вирулентность» встречались только в штаммах Beijing B0/W148, древних Beijing и LAM-RUS (SIT252/266). Выводы. Для эмерджентных, актуально или потенциально эпидемических вариантов M. tuberculosis генотипов LAM и Beijing, выявлены как филогенетически нейтральные, диагностические полиморфизмы, так и мутации в ряде генов вирулентности, адаптации, биосинтеза клеточной стенки, дыхания и липидного обмена.Tuberculosis is one of the re-emerging diseases that have epidemically spread in many regions worldwide. Understanding of the genetic basis for Mycobacterium tuberculosis adaptation to the human host is of a fundamental interest. The aim of this study was to identify molecular markers for significant genetic clusters of M. tuberculosis in Russia based on a whole genome and bioinformatics analysis. Whole genome sequencing and phylogenetic analysis were performed for a representative sample of M. tuberculosis strains of the East Asian lineage (ancient and modern sublineages of the Beijing genotype) and the Euro-American lineage (strains of LAM, T and S genotypes). The phylogenetic analysis of genomic data (4500 polymorphic nucleotide positions) allowed to identify strain clusters and to determine their specific single nucleotide polymorphisms (SNPs). Specifically, an evolutionarily “young” cluster was identified within the LAM-RUS branch, including strains of the SIT252 and SIT266 spoligotypes. Modern (subtypes B0 and 94-32) and ancient sublineages were identified within the Beijing genotype. Beijing and LAM cluster-specific SNPs were mainly found in gene categories “cell wall and cell processes” and “intermediary metabolism and respiration”. Variations in the genes of the “virulence” category were found only in strains of Beijing B0/W148, ancient Beijing and LAM-RUS (SIT252/266) groups. To conclude, phylogenetically neutral polymorphisms as well as mutations in virulence, adaptation, cell wall biosynthesis, respiration, and lipid metabolism genes were identified for emerging, potentially epidemic variants of the LAM and Beijing genotypes of M. tuberculosis.

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Evolution, Phylogenetics, and Phylogeography of Mycobacterium tuberculosis complex

Sola,

Mokrousov,

Sahal

et al. 2024

Genetics and Evolution of Infectious Diseases

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Early ancient sublineages of Mycobacterium tuberculosis Beijing genotype: unexpected clues from phylogenomics of the pathogen and human history

Cited by 19 publications

References 24 publications

Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

Применение полногеномного анализа для определения молекулярных маркеров значимых генетических кластеров Mycobacterium tuberculosis в России

Evolution, Phylogenetics, and Phylogeography of Mycobacterium tuberculosis complex

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