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Journal of Clinical Microbiology, September 2004, p. 4040-4049, Vol. 42, No. 9
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.9.4040-4049.2004

Definition of the Beijing/W Lineage of Mycobacterium tuberculosis on the Basis of Genetic Markers

Kristin Kremer,1 Judith R. Glynn,2 Troels Lillebaek,3 Stefan Niemann,4 Natalia E. Kurepina,5 Barry N. Kreiswirth,5 Pablo J. Bifani,6 and Dick van Soolingen1*

Mycobacteria Reference Unit, Diagnostic Laboratory of Infectious Diseases and Perinatal Screening, National Institute of Public Health and the Environment, Bilthoven, The Netherlands,1 London School of Hygiene and Tropical Medicine, London, United Kingdom,2 Statens Serum Institute, Copenhagen, Denmark,3 Forschungszentrum, Borstel, Germany,4 Public Health Research Institute, Newark, New Jersey,5 Institut Pasteur de Lille, Lille, France6

Received 3 December 2003/ Returned for modification 13 January 2004/ Accepted 18 May 2004

Mycobacterium tuberculosis Beijing genotype strains are highly prevalent in Asian countries and in the territory of the former Soviet Union. They are increasingly reported in other areas of the world and are frequently associated with tuberculosis outbreaks and drug resistance. Beijing genotype strains, including W strains, have been characterized by their highly similar multicopy IS6110 restriction fragment length polymorphism (RFLP) patterns, deletion of spacers 1 to 34 in the direct repeat region (Beijing spoligotype), and insertion of IS6110 in the genomic dnaA-dnaN locus. In this study the suitability and comparability of these three genetic markers to identify members of the Beijing lineage were evaluated. In a well-characterized collection of 1,020 M. tuberculosis isolates representative of the IS6110 RFLP genotypes found in The Netherlands, strains of two clades had spoligotypes characteristic of the Beijing lineage. A set of 19 Beijing reference RFLP patterns was selected to retrieve all Beijing strains from the Dutch database. These reference patterns gave a sensitivity of 98.1% and a specificity of 99.7% for identifying Beijing strains (defined by spoligotyping) in an international database of 1,084 strains. The usefulness of the reference patterns was also assessed with large DNA fingerprint databases in two other European countries and for identification strains from the W lineage found in the United States. A standardized definition for the identification of M. tuberculosis strains belonging to the Beijing/W lineage, as described in this work, will facilitate further studies on the spread and characterization of this widespread genotype family of M. tuberculosis strains.

* Corresponding author. Mailing address: Mycobacteria Reference Unit, Diagnostic Laboratory for Infectious Diseases and Perinatal Screening (LIS, pb22), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Phone: 31-30-2742363. Fax: 31-30-2744418. E-mail: d.van.soolingen{at}rivm.nl.

Journal of Clinical Microbiology, September 2004, p. 4040-4049, Vol. 42, No. 9
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.9.4040-4049.2004




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