Genomic signatures of drug resistance in highly resistant Mycobacterium tuberculosis strains of the early ancient sublineage of Beijing genotype in Russia

Mokrousov, Igor; Sinkov, V. V.; Vyazovaya, Anna; Pasechnik, Oksana; Solovieva, Natalia; Хромова, П. А.; Zhuravlev, Viacheslav; Огарков, О. Б.

doi:10.1016/j.ijantimicag.2020.106036

Cited by 10 publications

(26 citation statements)

References 43 publications

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“…Both could have descended from East Asian strains but circumstances and time of their likely Russian origin are elusive. A WGS study of Russian and East Asian Beijing strains [ 15 ] did not find a link between the Russian Beijing 1071-32 cluster (low-virulent strain 6691 in our study) and any location outside Russia. In contrast, a smaller cluster Beijing 14717-15 (hypervirulent strain 396 in our study) was located within the larger branch that included isolates from Korea.…”

Section: Discussioncontrasting

confidence: 76%

“…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%

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

Section: Methodsmentioning

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: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

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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“…Phylogenetic analysis of the ancient Beijing strains based on the WGS data obtained in our laboratory or retrieved from SRA NCBI, was described previously 15 and the list of the accession numbers of the analyzed genomes is provided in the same publication. In brief, short sequencing reads were mapped to the reference genome of M. tuberculosis H37Rv (NC_000962.3) by using the Burrows-Wheeler Aligner v. 0.7.12 21 .…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, a recent study in the Omsk province in Western Siberia detected a relatively elevated 10% prevalence of the ancient Beijing sublineage 14 . Most of those isolates belonged to the 1071-32-cluster (according to the MIRU-VNTRplus.org MLVA MtbC15-9 classification scheme) and also formed a monophyletic cluster within the WGS-based phylogenetic tree 15 . All Russian isolates of this cluster (from St. Petersburg, Omsk, and Samara) were multi-drug resistant (MDR) due to the specific signature of six mutations in rpoB , rpoC , katG , rpsL and embB .…”

Section: Introductionmentioning

confidence: 99%

Practical approach to detection and surveillance of emerging highly resistant Mycobacterium tuberculosis Beijing 1071-32-cluster

Mokrousov

Vyazovaya

Sinkov

et al. 2021

Sci Rep

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Ancient sublineage of the Mycobacterium tuberculosis Beijing genotype is endemic and prevalent in East Asia and rare in other world regions. While these strains are mainly drug susceptible, we recently identified a novel clonal group Beijing 1071-32 within this sublineage emerging in Siberia, Russia and present in other Russian regions. This cluster included only multi/extensive drug resistant (MDR/XDR) isolates. Based on the phylogenetic analysis of the available WGS data, we identified three synonymous SNPs in the genes Rv0144, Rv0373c, and Rv0334 that were specific for the Beijing 1071-32-cluster and developed a real-time PCR assay for their detection. Analysis of the 2375 genetically diverse M. tuberculosis isolates collected between 1996 and 2020 in different locations (European and Asian parts of Russia, former Soviet Union countries, Albania, Greece, China, Vietnam, Japan and Brazil), confirmed 100% specificity and sensitivity of this real-time PCR assay. Moreover, the epidemiological importance of this strain and the newly developed screening assay is further stressed by the fact that all identified Beijing 1071-32 isolates were found to exhibit MDR genotypic profiles with concomitant resistance to additional first-line drugs due to a characteristic signature of six mutations in rpoB450, rpoC485, katG315, katG335, rpsL43 and embB497. In conclusion, this study provides a set of three concordant SNPs for the detection and screening of Beijing 1071-32 isolates along with a validated real-time PCR assay easily deployable across multiple settings for the epidemiological tracking of this significant MDR cluster.

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Phylogenomics of the East Asian lineage of Mycobacterium tuberculosis

Shitikov,

Mokrousov,

Bespiatykh

2024

Phylogenomics

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Genomic signatures of drug resistance in highly resistant Mycobacterium tuberculosis strains of the early ancient sublineage of Beijing genotype in Russia

Cited by 10 publications

References 43 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

Practical approach to detection and surveillance of emerging highly resistant Mycobacterium tuberculosis Beijing 1071-32-cluster

Phylogenomics of the East Asian lineage of Mycobacterium tuberculosis

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