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Journal of Clinical Microbiology, May 2004, p. 1986-1993, Vol. 42, No. 5
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.5.1986-1993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Use of Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing To Examine Genetic Diversity of Mycobacterium tuberculosis in Singapore

Yong-Jiang Sun,1* Richard Bellamy,1 Ann S. G. Lee,2 Sze Ta Ng,1 Sindhu Ravindran,1 Sin-Yew Wong,1 Camille Locht,3 Philip Supply,3 and Nicholas I. Paton1

Department of Infectious Diseases, Tan Tock Seng Hospital,1 Division of Medical Sciences, National Cancer Centre, Singapore, Republic of Singapore,2 Laboratoire des Mécanismes Moléculaires de la Pathogenèse Bactérienne, INSERM U447, Institut Pasteur de Lille, Lille, France3

Received 9 December 2003/ Returned for modification 6 January 2004/ Accepted 28 January 2004

Strain typing using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) is a powerful tool for studying the epidemiology and genetic relationships of Mycobacterium tuberculosis isolates. For this study, isolates from 291 patients in Singapore were genotyped by this method. One hundred sixty-six distinct MIRU-VNTR patterns were detected. One hundred sixty-two strains were grouped into 1 of 35 different MIRU-VNTR clusters and 131 isolates were unique. In this sample collection, 9 of the 12 MIRU-VNTR loci were moderately or highly discriminative according to their allelic diversities. The Hunter-Gaston discriminatory index was 0.975, indicating the high power of discrimination of MIRU-VNTR typing. By direct comparisons with previously typed MIRU-VNTR patterns and by genetic relationship analyses, we could identify and clearly define four epidemic groups of M. tuberculosis in our sample, corresponding to the W/Beijing, East-Africa-Indian, Haarlem, and Delhi genotype families. Furthermore, MIRU-VNTR typing was able to clearly distinguish ancestral and modern M. tuberculosis strains as defined by TbD1 genomic deletion analysis. These results indicate that MIRU-VNTR typing can be a useful first-line tool for studying the genetic diversity of M. tuberculosis isolates in a large urban setting such as Singapore.

* Corresponding author. Mailing address: Infectious Disease Research Centre, Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Republic of Singapore. Phone: 65-6357-8959. Fax: 65-6256-7023. E-mail: Yong_Jiang_Sun{at}ttsh.com.sg.

Journal of Clinical Microbiology, May 2004, p. 1986-1993, Vol. 42, No. 5
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.5.1986-1993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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