Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster

Mokrousov I. Vyazovaya A. Shitikov E. Badleeva M. Belopolskaya O. Bespiatykh D. Gerasimova A. Ioannidis P. Jiao W. Khromova P. Masharsky A. Naizabayeva D. Papaventsis D. Pasechnik O. Perdigão J. Rastogi N. Shen A. Sinkov V. Skiba Y. Solovieva N. Tafaj S. Valcheva V. Kostyukova I. Zhdanova S. Zhuravlev V. Ogarkov O.
December 2023 BioMed Central Ltd

BMC Infectious Diseases
2023 #23 Issue 1

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.

Beijing genotype , Drug resistance , Mycobacterium tuberculosis , Virulence , Whole genome sequencing

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Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation
Henan International Joint Laboratory of Children’s Infectious Diseases, Henan Children’s Hospital, Children’s Hospital, Zhengzhou University, Zhengzhou Children’s Hospital, Zhengzhou, China
Department of Biomedicine and Genomics, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russian Federation
Department of Infectious Diseases, Dorji Banzarov Buryat State University, Ulan-Ude, Buryatia, Russian Federation
Resource Center Bio-bank Center, Research Park of St. Petersburg State University, St. Petersburg, Russian Federation
Laboratory of Genogeography, Vavilov Institute of General Genetics Russian Academy of Sciences Moscow, Moscow, Russian Federation
National Reference Laboratory for Mycobacteria, Sotiria Chest Diseases Hospital, Athens, Greece
National 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 Health, Beijing, China
Department of Epidemiology and Microbiology, Scientific Centre of the Family Health and Human Reproduction Problems, Irkutsk, Russian Federation
Laboratory of Molecular Biology, Almaty Branch of National Center for Biotechnology in Central Reference Laboratory, Almaty, Kazakhstan
Department of Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan
Department of Public Health, Omsk State Medical University, Omsk, Russian Federation
iMed.ULisboa – Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
WHO Supranational TB Reference Laboratory, Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France
Henan Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Children’s Hospital, Zhengzhou, China
St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russian Federation
National Mycobacteria Reference Laboratory, University Hospital Shefqet Ndroqi, Tirana, Albania
Laboratory of Molecular Genetics of Mycobacteria, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
Bacteriology laboratory, Clinical Tuberculosis Dispensary, Omsk, Russian Federation

Laboratory of Molecular Epidemiology and Evolutionary Genetics
Henan International Joint Laboratory of Children’s Infectious Diseases
Department of Biomedicine and Genomics
Department of Infectious Diseases
Resource Center Bio-bank Center
Laboratory of Genogeography
National Reference Laboratory for Mycobacteria
National Clinical Research Center for Respiratory Diseases
Department of Epidemiology and Microbiology
Laboratory of Molecular Biology
Department of Biotechnology
Department of Public Health
iMed.ULisboa – Instituto de Investigação do Medicamento
WHO Supranational TB Reference Laboratory
Henan Children’s Hospital
St. Petersburg Research Institute of Phthisiopulmonology
National Mycobacteria Reference Laboratory
Laboratory of Molecular Genetics of Mycobacteria
Bacteriology laboratory

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