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A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations

Denmark, a tuberculosis low burden country, still experiences significant active Mycobacterium tuberculosis (Mtb) transmission, especially with one specific genotype named Cluster 2/1112–15 (C2), the most prevalent lineage in Scandinavia. In addition to environmental factors, antibiotic resistance,...

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Autores principales: Folkvardsen, Dorte Bek, Norman, Anders, Andersen, Åse Bengård, Rasmussen, Erik Michael, Lillebaek, Troels, Jelsbak, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082827/
https://www.ncbi.nlm.nih.gov/pubmed/30089859
http://dx.doi.org/10.1038/s41598-018-30363-3
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author Folkvardsen, Dorte Bek
Norman, Anders
Andersen, Åse Bengård
Rasmussen, Erik Michael
Lillebaek, Troels
Jelsbak, Lars
author_facet Folkvardsen, Dorte Bek
Norman, Anders
Andersen, Åse Bengård
Rasmussen, Erik Michael
Lillebaek, Troels
Jelsbak, Lars
author_sort Folkvardsen, Dorte Bek
collection PubMed
description Denmark, a tuberculosis low burden country, still experiences significant active Mycobacterium tuberculosis (Mtb) transmission, especially with one specific genotype named Cluster 2/1112–15 (C2), the most prevalent lineage in Scandinavia. In addition to environmental factors, antibiotic resistance, and human genetics, there is increasing evidence that Mtb strain variation plays a role for the outcome of infection and disease. In this study, we explore the reasons for the success of the C2 genotype by analysing strain specific polymorphisms identified through whole genome sequencing of all C2 isolates identified in Denmark between 1992 and 2014 (n = 952), and the demographic distribution of C2. Of 234 non-synonymous (NS) monomorphic SNPs found in C2 in comparison with Mtb reference strain H37Rv, 23 were in genes previously reported to be involved in Mtb virulence. Of these 23 SNPs, three were specific for C2 including a NS mutation in a gene associated with hyper-virulence. We show that the genotype is readily transmitted to different ethnicities and is also found outside Denmark. Our data suggest that strain specific virulence factor variations are important for the success of the C2 genotype. These factors, likely in combination with poor TB control, seem to be the main drivers of C2 success.
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spelling pubmed-60828272018-08-10 A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations Folkvardsen, Dorte Bek Norman, Anders Andersen, Åse Bengård Rasmussen, Erik Michael Lillebaek, Troels Jelsbak, Lars Sci Rep Article Denmark, a tuberculosis low burden country, still experiences significant active Mycobacterium tuberculosis (Mtb) transmission, especially with one specific genotype named Cluster 2/1112–15 (C2), the most prevalent lineage in Scandinavia. In addition to environmental factors, antibiotic resistance, and human genetics, there is increasing evidence that Mtb strain variation plays a role for the outcome of infection and disease. In this study, we explore the reasons for the success of the C2 genotype by analysing strain specific polymorphisms identified through whole genome sequencing of all C2 isolates identified in Denmark between 1992 and 2014 (n = 952), and the demographic distribution of C2. Of 234 non-synonymous (NS) monomorphic SNPs found in C2 in comparison with Mtb reference strain H37Rv, 23 were in genes previously reported to be involved in Mtb virulence. Of these 23 SNPs, three were specific for C2 including a NS mutation in a gene associated with hyper-virulence. We show that the genotype is readily transmitted to different ethnicities and is also found outside Denmark. Our data suggest that strain specific virulence factor variations are important for the success of the C2 genotype. These factors, likely in combination with poor TB control, seem to be the main drivers of C2 success. Nature Publishing Group UK 2018-08-08 /pmc/articles/PMC6082827/ /pubmed/30089859 http://dx.doi.org/10.1038/s41598-018-30363-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Folkvardsen, Dorte Bek
Norman, Anders
Andersen, Åse Bengård
Rasmussen, Erik Michael
Lillebaek, Troels
Jelsbak, Lars
A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title_full A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title_fullStr A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title_full_unstemmed A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title_short A Major Mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: Exploring gene profile virulence explanations
title_sort major mycobacterium tuberculosis outbreak caused by one specific genotype in a low-incidence country: exploring gene profile virulence explanations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082827/
https://www.ncbi.nlm.nih.gov/pubmed/30089859
http://dx.doi.org/10.1038/s41598-018-30363-3
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