title: Can 15-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis provide insight into the evolution of Mycobacterium tuberculosis?
abstract: The phylogeny and evolution of the bacterium Mycobacterium tuberculosis is still poorly understood despite the application of a variety of molecular techniques. We analyzed 469 M. tuberculosis and 49 Mycobacterium bovis isolates to evaluate if the mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR) commonly used for epidemiological studies can define the phylogeny of the M. tuberculosis complex. This population was characterized by previously identified silent single-nucleotide polymorphisms (sSNPs) or by a macroarray based on these sSNPs that was developed in this study. MIRU-VNTR phylogenetic codes capable of differentiating between phylogenetic lineages were identified. Overall, there was 90.9% concordance between the lineages of isolates as defined by the MIRU-VNTR and sSNP analyses. The MIRU-VNTR phylogenetic code was unique to M. bovis and was not observed in any M. tuberculosis isolates. The codes were able to differentiate between different M. tuberculosis strain families such as Beijing, Delhi, and East African-Indian. Discrepant isolates with similar but not identical MIRU-VNTR codes often displayed a stepwise trend suggestive of bidirectional evolution. A lineage-specific panel of MIRU-VNTR can be used to subdivide each lineage for epidemiological purposes. MIRU-VNTR is a valuable tool for phylogenetic studies and could define an evolutionarily uncharacterized population of M. tuberculosis complex organisms.
authors.affiliation: Mycobacterium Reference Unit, Health Protection Agency, Barts and The London Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gibson
authors.forename: Timothy
authors.initials: T
authors.lastname: Brown
authors.forename: Lucy
authors.initials: L
authors.lastname: Baker
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D015342:DNA Probes; D019143:Evolution, Molecular; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D018598:Minisatellite Repeats; D009163:Mycobacterium bovis / Q000145:classification / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D015203:Reproducibility of Results
chemical_list: D017931:DNA Primers; D015342:DNA Probes