Open AccessA 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
Author(s) -
M. Carmen Garcia Pelayo,
Swapna Uplekar,
Andrew Keniry,
Pablo Mendoza Lopez,
Thierry Garnier,
Javier Nuñez Garcia,
Laura Boschiroli,
Xiangmei Zhou,
Julian Parkhill,
Noel H. Smith,
R. Glyn Hewinson,
Stewart T. Cole,
Stephen V. Gordon
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01099-08
Subject(s) - mycobacterium bovis , biology , single nucleotide polymorphism , virulence , genetics , phylogenetic tree , bcg vaccine , genotype , virology , mycobacterium tuberculosis , tuberculosis , microbiology and biotechnology , vaccination , gene , medicine , pathology
To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccineMycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains ofMycobacterium bovis andM. bovis BCG. SNPs were assayed inM. 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 virulentM. 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 virulentM. 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 virulentM. bovis strains and the attenuated BCG strain that will underpin future functional analyses.