High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.

Recently, the diversity of the Mycobacterium tuberculosis complex (MTBC) population structure has been described in detail. Based on geographical separation and specific host pathogen co-evolution shaping MTBC virulence traits, at least 20 major lineages/genotypes have evolved finally leading to a c...

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Autores principales:	Susanne Homolka, Michaela Projahn, Silke Feuerriegel, Tanja Ubben, Roland Diel, Ulrich Nübel, Stefan Niemann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/479f3d36022c456e8d5fbd9324971133
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spelling	oai:doaj.org-article:479f3d36022c456e8d5fbd93249711332021-11-18T07:13:33ZHigh resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.1932-620310.1371/journal.pone.0039855https://doaj.org/article/479f3d36022c456e8d5fbd93249711332012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768315/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recently, the diversity of the Mycobacterium tuberculosis complex (MTBC) population structure has been described in detail. Based on geographical separation and specific host pathogen co-evolution shaping MTBC virulence traits, at least 20 major lineages/genotypes have evolved finally leading to a clear influence of strain genetic background on transmissibility, clinical presentation/outcome, and resistance development. Therefore, high resolution genotyping for characterization of strains in larger studies is mandatory for understanding mechanisms of host-pathogen-interaction and to improve tuberculosis (TB) control. Single nucleotide polymorphisms (SNPs) represent the most reliable markers for lineage classification of clinical isolates due to the low levels of homoplasy, however their use is hampered either by low discriminatory power or by the need to analyze a large number of genes to achieve higher resolution. Therefore, we carried out de novo sequencing of 26 genes (approx. 20000 bp per strain) in a reference collection of MTBC strains including all major genotypes to define a highly discriminatory gene set. Overall, 161 polymorphisms were detected of which 59 are genotype-specific, while 13 define deeper branches such as the Euro-American lineage. Unbiased investigation of the most variable set of 11 genes in a population based strain collection (one year, city of Hamburg, Germany) confirmed the validity of SNP analysis as all strains were classified with high accuracy. Taken together, we defined a diagnostic algorithm which allows the identification of 17 MTBC phylogenetic lineages with high confidence for the first time by sequencing analysis of just five genes. In conclusion, the diagnostic algorithm developed in our study is likely to open the door for a low cost high resolution sequence/SNP based differentiation of the MTBC with a very high specificity. High throughput assays can be established which will be needed for large association studies that are mandatory for detailed investigation of host-pathogen-interaction during TB infection.Susanne HomolkaMichaela ProjahnSilke FeuerriegelTanja UbbenRoland DielUlrich NübelStefan NiemannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e39855 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanne Homolka Michaela Projahn Silke Feuerriegel Tanja Ubben Roland Diel Ulrich Nübel Stefan Niemann High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
description	Recently, the diversity of the Mycobacterium tuberculosis complex (MTBC) population structure has been described in detail. Based on geographical separation and specific host pathogen co-evolution shaping MTBC virulence traits, at least 20 major lineages/genotypes have evolved finally leading to a clear influence of strain genetic background on transmissibility, clinical presentation/outcome, and resistance development. Therefore, high resolution genotyping for characterization of strains in larger studies is mandatory for understanding mechanisms of host-pathogen-interaction and to improve tuberculosis (TB) control. Single nucleotide polymorphisms (SNPs) represent the most reliable markers for lineage classification of clinical isolates due to the low levels of homoplasy, however their use is hampered either by low discriminatory power or by the need to analyze a large number of genes to achieve higher resolution. Therefore, we carried out de novo sequencing of 26 genes (approx. 20000 bp per strain) in a reference collection of MTBC strains including all major genotypes to define a highly discriminatory gene set. Overall, 161 polymorphisms were detected of which 59 are genotype-specific, while 13 define deeper branches such as the Euro-American lineage. Unbiased investigation of the most variable set of 11 genes in a population based strain collection (one year, city of Hamburg, Germany) confirmed the validity of SNP analysis as all strains were classified with high accuracy. Taken together, we defined a diagnostic algorithm which allows the identification of 17 MTBC phylogenetic lineages with high confidence for the first time by sequencing analysis of just five genes. In conclusion, the diagnostic algorithm developed in our study is likely to open the door for a low cost high resolution sequence/SNP based differentiation of the MTBC with a very high specificity. High throughput assays can be established which will be needed for large association studies that are mandatory for detailed investigation of host-pathogen-interaction during TB infection.
format	article
author	Susanne Homolka Michaela Projahn Silke Feuerriegel Tanja Ubben Roland Diel Ulrich Nübel Stefan Niemann
author_facet	Susanne Homolka Michaela Projahn Silke Feuerriegel Tanja Ubben Roland Diel Ulrich Nübel Stefan Niemann
author_sort	Susanne Homolka
title	High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
title_short	High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
title_full	High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
title_fullStr	High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
title_full_unstemmed	High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
title_sort	high resolution discrimination of clinical mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/479f3d36022c456e8d5fbd9324971133
work_keys_str_mv	AT susannehomolka highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT michaelaprojahn highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT silkefeuerriegel highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT tanjaubben highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT rolanddiel highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT ulrichnubel highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms AT stefanniemann highresolutiondiscriminationofclinicalmycobacteriumtuberculosiscomplexstrainsbasedonsinglenucleotidepolymorphisms
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High resolution discrimination of clinical Mycobacterium tuberculosis complex strains based on single nucleotide polymorphisms.

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