| A comprehensive survey of single nucleotide polymorphisms (SNPs) across Mycobacterium bovis strains and M. bovis BCG vaccine strains refines the genealogy and defines a minimal set of SNPs that separate virulent M. bovis strains and M. bovis BCG strains. | |
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MedLine Citation:
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PMID: 19289514 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccine Mycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains of Mycobacterium bovis and M. bovis BCG. SNPs were assayed in M. bovis isolates from France and the United Kingdom and from different BCG vaccines in order to identify those that arose during the attenuation process which gave rise to BCG. Informative data sets were obtained for 658 SNPs from 21 virulent M. bovis strains and 13 BCG strains; these SNPs showed phylogenetic clustering that was consistent with the geographical origin of the strains and previous schemes for BCG genealogies. The data revealed a closer relationship between BCG Tice and BCG Pasteur than was previously appreciated, while we were able to position BCG Beijing within a grouping of BCG Denmark-derived strains. Only 186 SNPs were identified between virulent M. bovis strains and all BCG strains, with 115 nonsynonymous SNPs affecting important functions such as global regulators, transcriptional factors, and central metabolism, which might impact on virulence. We therefore refine previous genealogies of BCG vaccines and define a minimal set of SNPs between virulent M. bovis strains and the attenuated BCG strain that will underpin future functional analyses. |
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Authors:
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M Carmen Garcia Pelayo; Swapna Uplekar; Andrew Keniry; Pablo Mendoza Lopez; Thierry Garnier; Javier Nunez Garcia; Laura Boschiroli; Xiangmei Zhou; Julian Parkhill; Noel Smith; R Glyn Hewinson; Stewart T Cole; Stephen V Gordon |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-16 |
Journal Detail:
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Title: Infection and immunity Volume: 77 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-20 Completed Date: 2009-05-08 Revised Date: 2010-09-22 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 2230-8 Citation Subset: IM |
Affiliation:
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School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Dublin 4, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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BCG Vaccine
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genetics* Cluster Analysis DNA Fingerprinting DNA, Bacterial / genetics France Genetic Markers Genome, Bacterial* Great Britain Mutation, Missense Mycobacterium bovis / classification*, genetics*, isolation & purification, pathogenicity Phylogeny Point Mutation Polymorphism, Single Nucleotide* Vaccines, Attenuated / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CPA1497//Biotechnology and Biological Sciences Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/BCG Vaccine; 0/DNA, Bacterial; 0/Genetic Markers; 0/Vaccines, Attenuated |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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