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Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia
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...
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| Published in: | Emerging microbes & infections 2021-01, Vol.10 (1), p.1691-1701 |
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| creator | Vinogradova, Tatiana Dogonadze, Marine Zabolotnykh, Natalia Badleeva, Maria Yarusova, Irina Vyazovaya, Anna Gerasimova, Alena Zhdanova, Svetlana Vitovskaya, Maria Solovieva, Natalia Pasechnik, Oksana Ogarkov, Oleg Mokrousov, Igor |
| description | 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. |
| doi_str_mv | 10.1080/22221751.2021.1967704 |
| format | article |
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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.</description><identifier>ISSN: 2222-1751</identifier><identifier>EISSN: 2222-1751</identifier><identifier>DOI: 10.1080/22221751.2021.1967704</identifier><identifier>PMID: 34380361</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Antitubercular Agents - pharmacology ; Beijing ; Beijing genotype ; Disease Models, Animal ; DNA, Bacterial - genetics ; Drug Resistance, Multiple, Bacterial ; epidemic ; Epidemics ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Microbial Sensitivity Tests ; mouse model ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - pathogenicity ; Original ; Russia - epidemiology ; Tuberculosis, Multidrug-Resistant - epidemiology ; Tuberculosis, Multidrug-Resistant - mortality ; Virulence</subject><ispartof>Emerging microbes & infections, 2021-01, Vol.10 (1), p.1691-1701</ispartof><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2021</rights><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2021 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-2f87c2e676da7f2fb3633edd3f8e409d0289790a3433563d29885a7220a45a5e3</citedby><cites>FETCH-LOGICAL-c534t-2f87c2e676da7f2fb3633edd3f8e409d0289790a3433563d29885a7220a45a5e3</cites><orcidid>0000-0001-5924-0576</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381949/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381949/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27535,27957,27958,53827,53829,59498,59499</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34380361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vinogradova, Tatiana</creatorcontrib><creatorcontrib>Dogonadze, Marine</creatorcontrib><creatorcontrib>Zabolotnykh, Natalia</creatorcontrib><creatorcontrib>Badleeva, Maria</creatorcontrib><creatorcontrib>Yarusova, Irina</creatorcontrib><creatorcontrib>Vyazovaya, Anna</creatorcontrib><creatorcontrib>Gerasimova, Alena</creatorcontrib><creatorcontrib>Zhdanova, Svetlana</creatorcontrib><creatorcontrib>Vitovskaya, Maria</creatorcontrib><creatorcontrib>Solovieva, Natalia</creatorcontrib><creatorcontrib>Pasechnik, Oksana</creatorcontrib><creatorcontrib>Ogarkov, Oleg</creatorcontrib><creatorcontrib>Mokrousov, Igor</creatorcontrib><title>Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia</title><title>Emerging microbes & infections</title><addtitle>Emerg Microbes Infect</addtitle><description>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.</description><subject>Animals</subject><subject>Antitubercular Agents - pharmacology</subject><subject>Beijing</subject><subject>Beijing genotype</subject><subject>Disease Models, Animal</subject><subject>DNA, Bacterial - genetics</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>epidemic</subject><subject>Epidemics</subject><subject>Genotype</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbial Sensitivity Tests</subject><subject>mouse model</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - pathogenicity</subject><subject>Original</subject><subject>Russia - epidemiology</subject><subject>Tuberculosis, Multidrug-Resistant - epidemiology</subject><subject>Tuberculosis, Multidrug-Resistant - mortality</subject><subject>Virulence</subject><issn>2222-1751</issn><issn>2222-1751</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>DOA</sourceid><recordid>eNp9kU1vEzEQhlcIRKvQnwDykQMJ_lx7LwhUpVCpCAnB2Zp47cSVdx1sb2H_PQ5Jq_bCXGy9M_OMx2_TvCZ4RbDC72kNIgVZUUzJinStlJg_a84P-vKQeP7oftZc5HyLa0jccsJfNmeMM4VZS84bv_5Tkh1smFGwZQcBwdij3by36c6nKdixoK-ziRswxSY_DahMG5vMFGL2GeWSwI_IhCnXNKqgtPXjFlXtChJaQy7v0PcpZw-vmhcOQrYXp3PR_Lxa_7j8srz59vn68tPN0gjGy5I6JQ21rWx7kI66DWsZs33PnLIcdz2mqpMdhroCEy3raaeUAEkpBi5AWLZoro_cPsKt3ic_QJp1BK__CTFtNaTiTbAanJMKK9FBTzinAMRKRTsrDOfWUVJZH46s_bQZbG_qbyQIT6BPM6Pf6W2804op0vGuAt6eACn-mmwuevDZ2BBgtHHKmooWKyZV3WbRiGOpSTHnZN3DGIL1wXV977o-uK5Prte-N4_f-NB173Et-Hgs8KOLaYDfMYVeF5hDTC7BaHzW7P8z_gL6P71N</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Vinogradova, Tatiana</creator><creator>Dogonadze, Marine</creator><creator>Zabolotnykh, Natalia</creator><creator>Badleeva, Maria</creator><creator>Yarusova, Irina</creator><creator>Vyazovaya, Anna</creator><creator>Gerasimova, Alena</creator><creator>Zhdanova, Svetlana</creator><creator>Vitovskaya, Maria</creator><creator>Solovieva, Natalia</creator><creator>Pasechnik, Oksana</creator><creator>Ogarkov, Oleg</creator><creator>Mokrousov, Igor</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5924-0576</orcidid></search><sort><creationdate>20210101</creationdate><title>Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia</title><author>Vinogradova, Tatiana ; Dogonadze, Marine ; Zabolotnykh, Natalia ; Badleeva, Maria ; Yarusova, Irina ; Vyazovaya, Anna ; Gerasimova, Alena ; Zhdanova, Svetlana ; Vitovskaya, Maria ; Solovieva, Natalia ; Pasechnik, Oksana ; Ogarkov, Oleg ; Mokrousov, Igor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-2f87c2e676da7f2fb3633edd3f8e409d0289790a3433563d29885a7220a45a5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antitubercular Agents - pharmacology</topic><topic>Beijing</topic><topic>Beijing genotype</topic><topic>Disease Models, Animal</topic><topic>DNA, Bacterial - genetics</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>epidemic</topic><topic>Epidemics</topic><topic>Genotype</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbial Sensitivity Tests</topic><topic>mouse model</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - pathogenicity</topic><topic>Original</topic><topic>Russia - epidemiology</topic><topic>Tuberculosis, Multidrug-Resistant - epidemiology</topic><topic>Tuberculosis, Multidrug-Resistant - mortality</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vinogradova, Tatiana</creatorcontrib><creatorcontrib>Dogonadze, Marine</creatorcontrib><creatorcontrib>Zabolotnykh, Natalia</creatorcontrib><creatorcontrib>Badleeva, Maria</creatorcontrib><creatorcontrib>Yarusova, Irina</creatorcontrib><creatorcontrib>Vyazovaya, Anna</creatorcontrib><creatorcontrib>Gerasimova, Alena</creatorcontrib><creatorcontrib>Zhdanova, Svetlana</creatorcontrib><creatorcontrib>Vitovskaya, Maria</creatorcontrib><creatorcontrib>Solovieva, Natalia</creatorcontrib><creatorcontrib>Pasechnik, Oksana</creatorcontrib><creatorcontrib>Ogarkov, Oleg</creatorcontrib><creatorcontrib>Mokrousov, Igor</creatorcontrib><collection>Taylor & Francis Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Emerging microbes & infections</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vinogradova, Tatiana</au><au>Dogonadze, Marine</au><au>Zabolotnykh, Natalia</au><au>Badleeva, Maria</au><au>Yarusova, Irina</au><au>Vyazovaya, Anna</au><au>Gerasimova, Alena</au><au>Zhdanova, Svetlana</au><au>Vitovskaya, Maria</au><au>Solovieva, Natalia</au><au>Pasechnik, Oksana</au><au>Ogarkov, Oleg</au><au>Mokrousov, Igor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia</atitle><jtitle>Emerging microbes & infections</jtitle><addtitle>Emerg Microbes Infect</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>10</volume><issue>1</issue><spage>1691</spage><epage>1701</epage><pages>1691-1701</pages><issn>2222-1751</issn><eissn>2222-1751</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Supplemental data for this article can be accessed at https://doi.org/10.1080/22221751.2021.1967704.</notes><abstract>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.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>34380361</pmid><doi>10.1080/22221751.2021.1967704</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5924-0576</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antitubercular Agents - pharmacology Beijing Beijing genotype Disease Models, Animal DNA, Bacterial - genetics Drug Resistance, Multiple, Bacterial epidemic Epidemics Genotype Male Mice Mice, Inbred C57BL Microbial Sensitivity Tests mouse model Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - pathogenicity Original Russia - epidemiology Tuberculosis, Multidrug-Resistant - epidemiology Tuberculosis, Multidrug-Resistant - mortality Virulence |
| title | Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia |
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