Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster
Abstract Background . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal stra...
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BMC
2023-06-01
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Online Access: | https://doi.org/10.1186/s12879-023-08413-7 |
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author | Igor Mokrousov Anna Vyazovaya Egor Shitikov Maria Badleeva Olesya Belopolskaya Dmitry Bespiatykh Alena Gerasimova Panayotis Ioannidis Weiwei Jiao Polina Khromova Aleksey Masharsky Dinara Naizabayeva Dimitrios Papaventsis Oksana Pasechnik João Perdigão Nalin Rastogi Adong Shen Viacheslav Sinkov Yuriy Skiba Natalia Solovieva Silva Tafaj Violeta Valcheva Irina Kostyukova Svetlana Zhdanova Viacheslav Zhuravlev Oleg Ogarkov |
author_facet | Igor Mokrousov Anna Vyazovaya Egor Shitikov Maria Badleeva Olesya Belopolskaya Dmitry Bespiatykh Alena Gerasimova Panayotis Ioannidis Weiwei Jiao Polina Khromova Aleksey Masharsky Dinara Naizabayeva Dimitrios Papaventsis Oksana Pasechnik João Perdigão Nalin Rastogi Adong Shen Viacheslav Sinkov Yuriy Skiba Natalia Solovieva Silva Tafaj Violeta Valcheva Irina Kostyukova Svetlana Zhdanova Viacheslav Zhuravlev Oleg Ogarkov |
author_sort | Igor Mokrousov |
collection | DOAJ |
description | Abstract Background . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal strain circulating in the Far Eastern region of Russia. Here, we aimed to analyze its pathogenomic features and phylogeographic pattern. Results . The study collection included M. tuberculosis DNA collected between 1996 and 2020 in different world regions. The bacterial DNA was subjected to genotyping and whole genome sequencing followed by bioinformatics and phylogenetic analysis. The PCR-based assay to detect specific SNPs of the Beijing 14717-15-cluster was developed and used for its screening in the global collections. Phylogenomic and phylogeographic analysis confirmed endemic prevalence of the Beijing 14717-15-cluster in the Asian part of Russia, and distant common ancestor with isolates from Korea (> 115 SNPs). The Beijing 14717-15-cluster isolates had two common resistance mutations RpsL Lys88Arg and KatG Ser315Thr and belonged to spoligotype SIT269. The Russian isolates of this cluster were from the Asian Russia while 4 isolates were from the Netherlands and Spain. The cluster-specific SNPs that significantly affect the protein function were identified in silico in genes within different categories (lipid metabolism, regulatory proteins, intermediary metabolism and respiration, PE/PPE, cell wall and cell processes). Conclusions . We developed a simple method based on real-time PCR to detect clinically significant MDR and hypervirulent Beijing 14717-15-cluster. Most of the identified cluster-specific mutations were previously unreported and could potentially be associated with increased pathogenic properties of this hypervirulent M. tuberculosis strain. Further experimental study to assess the pathobiological role of these mutations is warranted. |
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language | English |
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spelling | doaj.art-b4323bb60b4e4282aa0b379367bd0c072023-06-25T11:10:05ZengBMCBMC Infectious Diseases1471-23342023-06-0123111110.1186/s12879-023-08413-7Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain clusterIgor Mokrousov0Anna Vyazovaya1Egor Shitikov2Maria Badleeva3Olesya Belopolskaya4Dmitry Bespiatykh5Alena Gerasimova6Panayotis Ioannidis7Weiwei Jiao8Polina Khromova9Aleksey Masharsky10Dinara Naizabayeva11Dimitrios Papaventsis12Oksana Pasechnik13João Perdigão14Nalin Rastogi15Adong Shen16Viacheslav Sinkov17Yuriy Skiba18Natalia Solovieva19Silva Tafaj20Violeta Valcheva21Irina Kostyukova22Svetlana Zhdanova23Viacheslav Zhuravlev24Oleg Ogarkov25Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur InstituteLaboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur InstituteDepartment of Biomedicine and Genomics, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological AgencyDepartment of Infectious Diseases, Dorji Banzarov Buryat State UniversityResource Center Bio-bank Center, Research Park of St. Petersburg State UniversityDepartment of Biomedicine and Genomics, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological AgencyLaboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur InstituteNational Reference Laboratory for Mycobacteria, Sotiria Chest Diseases HospitalNational Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Disease, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children’s HealthDepartment of Epidemiology and Microbiology, Scientific Centre of the Family Health and Human Reproduction ProblemsResource Center Bio-bank Center, Research Park of St. Petersburg State UniversityLaboratory of Molecular Biology, Almaty Branch of National Center for Biotechnology in Central Reference LaboratoryNational Reference Laboratory for Mycobacteria, Sotiria Chest Diseases HospitalDepartment of Public Health, Omsk State Medical UniversityiMed.ULisboa – Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de LisboaWHO Supranational TB Reference Laboratory, Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de la GuadeloupeNational Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Disease, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children’s HealthDepartment of Epidemiology and Microbiology, Scientific Centre of the Family Health and Human Reproduction ProblemsLaboratory of Molecular Biology, Almaty Branch of National Center for Biotechnology in Central Reference LaboratorySt. Petersburg Research Institute of PhthisiopulmonologyNational Mycobacteria Reference Laboratory, University Hospital Shefqet NdroqiLaboratory of Molecular Genetics of Mycobacteria, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of SciencesBacteriology laboratory, Clinical Tuberculosis DispensaryDepartment of Epidemiology and Microbiology, Scientific Centre of the Family Health and Human Reproduction ProblemsSt. Petersburg Research Institute of PhthisiopulmonologyDepartment of Epidemiology and Microbiology, Scientific Centre of the Family Health and Human Reproduction ProblemsAbstract Background . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal strain circulating in the Far Eastern region of Russia. Here, we aimed to analyze its pathogenomic features and phylogeographic pattern. Results . The study collection included M. tuberculosis DNA collected between 1996 and 2020 in different world regions. The bacterial DNA was subjected to genotyping and whole genome sequencing followed by bioinformatics and phylogenetic analysis. The PCR-based assay to detect specific SNPs of the Beijing 14717-15-cluster was developed and used for its screening in the global collections. Phylogenomic and phylogeographic analysis confirmed endemic prevalence of the Beijing 14717-15-cluster in the Asian part of Russia, and distant common ancestor with isolates from Korea (> 115 SNPs). The Beijing 14717-15-cluster isolates had two common resistance mutations RpsL Lys88Arg and KatG Ser315Thr and belonged to spoligotype SIT269. The Russian isolates of this cluster were from the Asian Russia while 4 isolates were from the Netherlands and Spain. The cluster-specific SNPs that significantly affect the protein function were identified in silico in genes within different categories (lipid metabolism, regulatory proteins, intermediary metabolism and respiration, PE/PPE, cell wall and cell processes). Conclusions . We developed a simple method based on real-time PCR to detect clinically significant MDR and hypervirulent Beijing 14717-15-cluster. Most of the identified cluster-specific mutations were previously unreported and could potentially be associated with increased pathogenic properties of this hypervirulent M. tuberculosis strain. Further experimental study to assess the pathobiological role of these mutations is warranted.https://doi.org/10.1186/s12879-023-08413-7Mycobacterium tuberculosisWhole genome sequencingVirulenceDrug resistanceBeijing genotype |
spellingShingle | Igor Mokrousov Anna Vyazovaya Egor Shitikov Maria Badleeva Olesya Belopolskaya Dmitry Bespiatykh Alena Gerasimova Panayotis Ioannidis Weiwei Jiao Polina Khromova Aleksey Masharsky Dinara Naizabayeva Dimitrios Papaventsis Oksana Pasechnik João Perdigão Nalin Rastogi Adong Shen Viacheslav Sinkov Yuriy Skiba Natalia Solovieva Silva Tafaj Violeta Valcheva Irina Kostyukova Svetlana Zhdanova Viacheslav Zhuravlev Oleg Ogarkov Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster BMC Infectious Diseases Mycobacterium tuberculosis Whole genome sequencing Virulence Drug resistance Beijing genotype |
title | Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster |
title_full | Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster |
title_fullStr | Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster |
title_full_unstemmed | Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster |
title_short | Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster |
title_sort | insight into pathogenomics and phylogeography of hypervirulent and highly lethal mycobacterium tuberculosis strain cluster |
topic | Mycobacterium tuberculosis Whole genome sequencing Virulence Drug resistance Beijing genotype |
url | https://doi.org/10.1186/s12879-023-08413-7 |
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