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PHYLOGENOMIC AND GENOMIC ANALYSIS REVEALS UNIQUE AND SHARED GENETIC SIGNATURES OF MYCOBACTERIUM KANSASII COMPLEX SPECIES
Produção científica do Laboratório de Genética Molecular de Microrganismos.
Impact Statement: Mycobacterium kansasii complex (MKC) is a group of closely related non-tuberculous mycobacteria species, recognized as a significant source of human infection. Species belonging to the MKC may present a broad spectrum of virulence, antimicrobial resistance and pathogenicity and there is a lack of knowledge about their genomic content related to these broad phenotypes. We have provided whole genomic sequencing DNA for 342 MKC isolates and, together with public data, investigated the MKC pangenome, mobilome, resistome, virulome and defence systems and show unique and shared genetic signatures within MKC species. Furthermore, with phylogenomic and Bayesian population analysis, we inferred the distribution and emergence of the Mycobacterium kansasii species lineages and sub-lineages. This study has considerably expanded the MKC available data, by providing genomic sequences of isolates from countries and global regions with unknown or poorly described MKC data until then.
Data Summary: Next generation sequencing (NGS) data generated in the study are available in the NCBI Sequence Read Archive (SRA) repository under the accession number PRJNA1048499 and the accession numbers for all data sets used are provided in Table S1 (available in the online version of this article).
Data Availability: All sequenced reads are available in BioProject PRJNA1048499. Supplementary tables 1 to 19 providing details of used data and results of this study are available on the Microbiology Figshare data repository platform: https://doi.org/10.6084/m9.figshare.26014465.v1.
Author
Machado Filho, Edson Silva
Vasconcellos, Sidra Ezidio Gonçalves
Gomes, Lia Lima
Souza, Marcos Paulo Catanho de
Ramos, Jesus Pais
Carvalho, Luciana Distásio de
Goldenberg, Telma
Redner, Paulo
Caldas, Paulo Cesar de Souza
Campos, Carlos Eduardo Dias
Dalcolmo, Margareth Maria Pretti
Lourenço, Maria Cristina da Silva
Lassounskaia, Elena
Mussi, Vinicius de Oliveira
Borges, Lizânia Spinassé
Vinhas, Solange Alves
Rigouts, Leen
Cogneau, Sari
Rijk, Pim de
Utpatel, Christian
Kaustova, Jarmila
Laan, Tridia van der
Neeling, Han de
Rastogi, Nalin
Levina, Klavdia
Kütt, Marge
Mokrousov, Igor
Zhuravlev, Viacheslav
Makhado, Ndivhu
Žolnir-Dovč, Manca
Jankovic, Vera
Waard, Jacobus de
Sisco, Maria Carolina
Soolingen, Dick van
Niemann, Stefan
Jong, Bouke C. de
Meehan, Conor J.
Suffys, Philip Noel
Vasconcellos, Sidra Ezidio Gonçalves
Gomes, Lia Lima
Souza, Marcos Paulo Catanho de
Ramos, Jesus Pais
Carvalho, Luciana Distásio de
Goldenberg, Telma
Redner, Paulo
Caldas, Paulo Cesar de Souza
Campos, Carlos Eduardo Dias
Dalcolmo, Margareth Maria Pretti
Lourenço, Maria Cristina da Silva
Lassounskaia, Elena
Mussi, Vinicius de Oliveira
Borges, Lizânia Spinassé
Vinhas, Solange Alves
Rigouts, Leen
Cogneau, Sari
Rijk, Pim de
Utpatel, Christian
Kaustova, Jarmila
Laan, Tridia van der
Neeling, Han de
Rastogi, Nalin
Levina, Klavdia
Kütt, Marge
Mokrousov, Igor
Zhuravlev, Viacheslav
Makhado, Ndivhu
Žolnir-Dovč, Manca
Jankovic, Vera
Waard, Jacobus de
Sisco, Maria Carolina
Soolingen, Dick van
Niemann, Stefan
Jong, Bouke C. de
Meehan, Conor J.
Suffys, Philip Noel
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Serviço de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Bacteriologia e Bioensaios. Rio de Janeiro, RJ, Brasil.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Campos dos Goytacazes, RJ, Brasil.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Campos dos Goytacazes, RJ, Brasil.
Universidade Federal do Espírito Santo. Centro de Ciências da Saúde. Departamento de Medicina Social. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.
Universidade Federal do Espírito Santo. Centro de Ciências da Saúde. Departamento de Medicina Social. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Research Center Borstel. Molecular and Experimental Mycobacteriology. Borstel, Germany / Partner Site Hamburg-Lübeck-Borstel-Riems. German Center for Infection Research. Borstel, Germany.
Regional Institute of Public Health. Department of Diagnostic Mycobacterioses. Ostrava, Czech Republic.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Institut Pasteur de Guadeloupe. TB and Mycobacteria Unit. Guadeloupe, France.
North Estonia Medical Centre. Microbiology Laboratory. Mycobacteriology Section. Tallinn, Estonia.
North Estonia Medical Centre. Microbiology Laboratory. Mycobacteriology Section. Tallinn, Estonia.
St. Petersburg Pasteur Institute. Laboratory of Molecular Epidemiology and Evolutionary Genetics. St. Petersburg, Russia.
St. Petersburg Research Institute of Phthisiopulmonology. St. Petersburg, Russia.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium / Sefako Makgatho Health Sciences University. Department of Microbiological Pathology. Pretoria, South Africa / Medical Microbiology. Dr. George Mukhari Tertiary Laboratory. National Health Laboratory Service. Pretoria, South Africa / University of Antwerp. Global Institute of Health. Antwerp, Belgium.
University Clinic of Respiratory and Allergic Diseases. National Reference Laboratory for Mycobacteria. Golnik, Slovenia.
Croatian National Institute of Public Health. Mycobacteria Reference Laboratory. Zagreb, Croatia.
Universidad Central de Venezuela. Servicio Autónomo Instituto de Biomedicina Dr. Jacinto Convit. Tuberculosis Department. Caracas, Venezuela / Universidad de Las Américas. One Health Research Group. Quito, Ecuador.
Universidad Central de Venezuela. Servicio Autónomo Instituto de Biomedicina Dr. Jacinto Convit. Tuberculosis Department. Caracas, Venezuela.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Research Center Borstel. Molecular and Experimental Mycobacteriology. Borstel, Germany / Partner Site Hamburg-Lübeck-Borstel-Riems. German Center for Infection Research. Borstel, Germany.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium / Nottingham Trent University. Department of Biosciences. Nottingham, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Laboratório de Referência Nacional para Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Serviço de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Bacteriologia e Bioensaios. Rio de Janeiro, RJ, Brasil.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Campos dos Goytacazes, RJ, Brasil.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Campos dos Goytacazes, RJ, Brasil.
Universidade Federal do Espírito Santo. Centro de Ciências da Saúde. Departamento de Medicina Social. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.
Universidade Federal do Espírito Santo. Centro de Ciências da Saúde. Departamento de Medicina Social. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Research Center Borstel. Molecular and Experimental Mycobacteriology. Borstel, Germany / Partner Site Hamburg-Lübeck-Borstel-Riems. German Center for Infection Research. Borstel, Germany.
Regional Institute of Public Health. Department of Diagnostic Mycobacterioses. Ostrava, Czech Republic.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Institut Pasteur de Guadeloupe. TB and Mycobacteria Unit. Guadeloupe, France.
North Estonia Medical Centre. Microbiology Laboratory. Mycobacteriology Section. Tallinn, Estonia.
North Estonia Medical Centre. Microbiology Laboratory. Mycobacteriology Section. Tallinn, Estonia.
St. Petersburg Pasteur Institute. Laboratory of Molecular Epidemiology and Evolutionary Genetics. St. Petersburg, Russia.
St. Petersburg Research Institute of Phthisiopulmonology. St. Petersburg, Russia.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium / Sefako Makgatho Health Sciences University. Department of Microbiological Pathology. Pretoria, South Africa / Medical Microbiology. Dr. George Mukhari Tertiary Laboratory. National Health Laboratory Service. Pretoria, South Africa / University of Antwerp. Global Institute of Health. Antwerp, Belgium.
University Clinic of Respiratory and Allergic Diseases. National Reference Laboratory for Mycobacteria. Golnik, Slovenia.
Croatian National Institute of Public Health. Mycobacteria Reference Laboratory. Zagreb, Croatia.
Universidad Central de Venezuela. Servicio Autónomo Instituto de Biomedicina Dr. Jacinto Convit. Tuberculosis Department. Caracas, Venezuela / Universidad de Las Américas. One Health Research Group. Quito, Ecuador.
Universidad Central de Venezuela. Servicio Autónomo Instituto de Biomedicina Dr. Jacinto Convit. Tuberculosis Department. Caracas, Venezuela.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Research Center Borstel. Molecular and Experimental Mycobacteriology. Borstel, Germany / Partner Site Hamburg-Lübeck-Borstel-Riems. German Center for Infection Research. Borstel, Germany.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium.
Institute of Tropical Medicine. Unit of Mycobacteriology. Antwerp, Belgium / Nottingham Trent University. Department of Biosciences. Nottingham, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Abstract
Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii (sensu stricto), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these nontuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii’s increased virulence and drug resistance.
Publisher
Microbiology Society
Citation
MACHADO FILHO, Edson Silva et al. Phylogenomic and genomic analysis reveals unique and shared genetic signatures of Mycobacterium kansasii complex species. Microbial Genomics, v. 10, n. 7, p. 1-16, 17 July 2024.DOI
10.1099/mgen.0.001266ISSN
2057-5858Notes
Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias.Produção científica do Laboratório de Genética Molecular de Microrganismos.
Impact Statement: Mycobacterium kansasii complex (MKC) is a group of closely related non-tuberculous mycobacteria species, recognized as a significant source of human infection. Species belonging to the MKC may present a broad spectrum of virulence, antimicrobial resistance and pathogenicity and there is a lack of knowledge about their genomic content related to these broad phenotypes. We have provided whole genomic sequencing DNA for 342 MKC isolates and, together with public data, investigated the MKC pangenome, mobilome, resistome, virulome and defence systems and show unique and shared genetic signatures within MKC species. Furthermore, with phylogenomic and Bayesian population analysis, we inferred the distribution and emergence of the Mycobacterium kansasii species lineages and sub-lineages. This study has considerably expanded the MKC available data, by providing genomic sequences of isolates from countries and global regions with unknown or poorly described MKC data until then.
Data Summary: Next generation sequencing (NGS) data generated in the study are available in the NCBI Sequence Read Archive (SRA) repository under the accession number PRJNA1048499 and the accession numbers for all data sets used are provided in Table S1 (available in the online version of this article).
Data Availability: All sequenced reads are available in BioProject PRJNA1048499. Supplementary tables 1 to 19 providing details of used data and results of this study are available on the Microbiology Figshare data repository platform: https://doi.org/10.6084/m9.figshare.26014465.v1.
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