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Journal of Clinical Microbiology, December 2007, p. 3891-3902, Vol. 45, No. 12
0095-1137/07/$08.00+0     doi:10.1128/JCM.01394-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Discovery of a Novel Mycobacterium tuberculosis Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil ^,

Luiz Claudio Oliveira Lazzarini,^1,2, Richard C. Huard,^1,, Neio L. Boechat,² Harrison M. Gomes,³ Maranibia C. Oelemann,³ Natalia Kurepina,⁴ Elena Shashkina,⁴ Fernanda C. Q. Mello,² Andrea L. Gibson,¹ Milena J. Virginio,³ Ana Grazia Marsico,² W. Ray Butler,⁵ Barry N. Kreiswirth,⁴ Philip N. Suffys,³ Jose Roberto Lapa e Silva,^1,2 and John L. Ho^1*

Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021,¹ Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590,² Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil, 21040-900,³ Public Health Research Institute, Newark, New Jersey 07103,⁴ Centers for Disease Control and Prevention, Atlanta, Georgia 30333⁵

Received 11 July 2007/ Returned for modification 1 September 2007/ Accepted 17 September 2007

The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD^Rio. Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD^Rio locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD^Rio strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD^Rio lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD^Rio strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD^Rio strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD^Rio M. tuberculosis.

Published ahead of print on 26 September 2007.

Supplemental material for this article may be found at http://jcm.asm.org/.

L.C.O.L. and R.C.H. contributed equally to this work.

Present address: Clinical Microbiology Service and Department of Pathology, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY 10032.

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