title: Clonal expansion of a globally disseminated lineage of Mycobacterium tuberculosis with low IS6110 copy numbers.
abstract: Knowledge of the clonal expansion of Mycobacterium tuberculosis and accurate identification of predominant evolutionary lineages in this species remain limited, especially with regard to low-IS6110-copy-number strains. In this study, 170 M. tuberculosis isolates with </=6 IS6110 insertions identified in Cape Town, South Africa, were characterized by principal genetic grouping, restriction fragment length polymorphism analysis, spoligotyping, IS6110 insertion site mapping, and variable-number tandem repeat (VNTR) typing. These analyses indicated that all but one of the isolates analyzed were members of principal genetic group 2 and of the same low-IS6110-copy-number lineage. The remaining isolate was a member of principal genetic group 1 and a different low-IS6110-copy-number lineage. Phylogenetic reconstruction suggests clonal expansion through sequential acquisition of additional IS6110 copies, expansion and contraction of VNTR sequences, and the deletion of specific direct-variable-repeat sequences. Furthermore, comparison of the genotypic data of 91 representative low-IS6110-copy-number isolates from Cape Town, other southern African regions, Europe, and the United States suggests that certain low-IS6110-copy-number strain spoligotypes and IS6110 fingerprints were acquired in the distant past. These clones have subsequently become widely disseminated and now play an important role in the global tuberculosis epidemic.
authors.affiliation: MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg, 7505, South Africa. RW1@SUN.AC.ZA
authors.forename: R M
authors.initials: RM
authors.lastname: Warren
authors.forename: T C
authors.initials: TC
authors.lastname: Victor
authors.forename: E M
authors.initials: EM
authors.lastname: Streicher
authors.forename: M
authors.initials: M
authors.lastname: Richardson
authors.forename: G D
authors.initials: GD
authors.lastname: van der Spuy
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.forename: V N
authors.initials: VN
authors.lastname: Chihota
authors.forename: C
authors.initials: C
authors.lastname: Locht
authors.forename: P
authors.initials: P
authors.lastname: Supply
authors.forename: P D
authors.initials: PD
authors.lastname: van Helden
mesh_terms: D004251:DNA Transposable Elements; D005060:Europe / Q000453:epidemiology; D019143:Evolution, Molecular; D018628:Gene Dosage; D006801:Humans; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics*; D009841:Oligonucleotides / Q000032:analysis; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology; D014481:United States / Q000453:epidemiology
chemical_list: D004251:DNA Transposable Elements; D009841:Oligonucleotides