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Mycobacteriology and Aerobic Actinomycetes

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

Luiz Claudio Oliveira Lazzarini, Richard C. Huard, Neio L. Boechat, Harrison M. Gomes, Maranibia C. Oelemann, Natalia Kurepina, Elena Shashkina, Fernanda C. Q. Mello, Andrea L. Gibson, Milena J. Virginio, Ana Grazia Marsico, W. Ray Butler, Barry N. Kreiswirth, Philip N. Suffys, Jose Roberto Lapa e Silva, John L. Ho
Luiz Claudio Oliveira Lazzarini
1Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021
2Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590
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Richard C. Huard
1Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021
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Neio L. Boechat
2Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590
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Harrison M. Gomes
3Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil, 21040-900
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Maranibia C. Oelemann
3Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil, 21040-900
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Natalia Kurepina
4Public Health Research Institute, Newark, New Jersey 07103
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Elena Shashkina
4Public Health Research Institute, Newark, New Jersey 07103
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Fernanda C. Q. Mello
2Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590
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Andrea L. Gibson
1Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021
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Milena J. Virginio
3Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil, 21040-900
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Ana Grazia Marsico
2Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590
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W. Ray Butler
5Centers for Disease Control and Prevention, Atlanta, Georgia 30333
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Barry N. Kreiswirth
4Public Health Research Institute, Newark, New Jersey 07103
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Philip N. Suffys
3Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil, 21040-900
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Jose Roberto Lapa e Silva
1Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021
2Institute of Thoracic Diseases, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21941-590
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John L. Ho
1Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021
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  • For correspondence: jlho@med.cornell.edu
DOI: 10.1128/JCM.01394-07
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ABSTRACT

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 RDRio. 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 RDRio 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 RDRio strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RDRio 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 RDRio 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 RDRio 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 RDRioM. tuberculosis.

  • Copyright © 2007 American Society for Microbiology
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Discovery of a Novel Mycobacterium tuberculosis Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil
Luiz Claudio Oliveira Lazzarini, Richard C. Huard, Neio L. Boechat, Harrison M. Gomes, Maranibia C. Oelemann, Natalia Kurepina, Elena Shashkina, Fernanda C. Q. Mello, Andrea L. Gibson, Milena J. Virginio, Ana Grazia Marsico, W. Ray Butler, Barry N. Kreiswirth, Philip N. Suffys, Jose Roberto Lapa e Silva, John L. Ho
Journal of Clinical Microbiology Dec 2007, 45 (12) 3891-3902; DOI: 10.1128/JCM.01394-07

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Discovery of a Novel Mycobacterium tuberculosis Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil
Luiz Claudio Oliveira Lazzarini, Richard C. Huard, Neio L. Boechat, Harrison M. Gomes, Maranibia C. Oelemann, Natalia Kurepina, Elena Shashkina, Fernanda C. Q. Mello, Andrea L. Gibson, Milena J. Virginio, Ana Grazia Marsico, W. Ray Butler, Barry N. Kreiswirth, Philip N. Suffys, Jose Roberto Lapa e Silva, John L. Ho
Journal of Clinical Microbiology Dec 2007, 45 (12) 3891-3902; DOI: 10.1128/JCM.01394-07
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KEYWORDS

Mycobacterium tuberculosis
Polymorphism, Genetic
tuberculosis

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