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

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

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2230-2238
Number of pages9
JournalInfection and Immunity
Volume77
Issue number5
Early online date17 Apr 2009
DOIs
Publication statusPublished - 01 May 2009

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