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Journal of Bacteriology, April 2003, p. 2555-2562, Vol. 185, No. 8
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.8.2555-2562.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Evolutionary Relationships among Strains of Mycobacterium tuberculosis with Few Copies of IS6110

Jeremy W. Dale,1* Hasan Al-Ghusein,2 Salim Al-Hashmi,1 Philip Butcher,2 Anne L. Dickens,3 Francis Drobniewski,4 Ken J. Forbes,5 Stephen H. Gillespie,3 Dianie Lamprecht,4 Timothy D. McHugh,3 Richard Pitman,6 Nalin Rastogi,7 Andrew T. Smith,1 Christophe Sola,7 and Hasan Yesilkaya5

School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH,1 Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 0RE,2 Department of Medical Microbiology, Royal Free and University College Medical School, London NW3 2PF,3 PHLS Mycobacterial Reference Unit, Public Health and Medical Microbiology, Guy's, Kings and St. Thomas' School of Medicine, London SE22 8QF,4 Department of Medical Microbiology, Aberdeen University, Foresterhill, Aberdeen AB25 2ZD,5 Respiratory Division, PHLS Communicable Disease Surveillance Centre, London NW9 5EQ, United Kingdom,6 Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, F-97165 Pointe-à-Pitre Cedex, Guadeloupe, France7

Received 25 September 2002/ Accepted 30 January 2003

Molecular typing of Mycobacterium tuberculosis by using IS6110 shows low discrimination when there are fewer than five copies of the insertion sequence. Using a collection of such isolates from a study of the epidemiology of tuberculosis in London, we have shown a substantial degree of congruence between IS6110 patterns and both spoligotype and PGRS type. This indicates that the IS6110 types mainly represent distinct families of strains rather than arising through the convergent insertion of IS6110 into favored positions. This is supported by identification of the genomic sites of the insertion of IS6110 in these strains. The combined data enable identification of the putative evolutionary relationships of these strains, comprising three lineages broadly associated with patients born in South Asia (India and Pakistan), Africa, and Europe, respectively. These lineages appear to be quite distinct from M. tuberculosis isolates with multiple copies of IS6110.

* Corresponding author. Mailing address: School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom. Phone: 44 1483 686484. Fax: 44 1483 300374. E-mail: j.dale{at}surrey.ac.uk.

Journal of Bacteriology, April 2003, p. 2555-2562, Vol. 185, No. 8
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.8.2555-2562.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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