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Journal of Clinical Microbiology, December 2004, p. 5774-5782, Vol. 42, No. 12
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.12.5774-5782.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Clonal Expansion of a Globally Disseminated Lineage of Mycobacterium tuberculosis with Low IS6110 Copy Numbers

R. M. Warren,1* T. C. Victor,1 E. M. Streicher,1 M. Richardson,1 G. D. van der Spuy,1 R. Johnson,1 V. N. Chihota,1 C. Locht,2 P. Supply,2 and P. D. van Helden1

MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa,1 Laboratoire des Mécanismes Moléculaires de la Pathogenèse Bactérienne, INSERM U629, Institut Pasteur de Lille, Lille, France2

Received 18 February 2004/ Returned for modification 9 June 2004/ Accepted 9 August 2004

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.

* Corresponding author. Mailing address: MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, University of Stellenbosch, P.O. Box 19063, Tygerberg, 7505, South Africa. Phone: 27-21-9389482. Fax: 27-21-9389476. E-mail: RW1{at}SUN.AC.ZA.

Journal of Clinical Microbiology, December 2004, p. 5774-5782, Vol. 42, No. 12
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.12.5774-5782.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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