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Comparative Genomics Uncovers Large Tandem Chromosomal Duplications in Mycobacterium Bovis BCG Pasteur

By Roland Brosch, Stephen V. Gordon, Carmen Buchrieser, Alexander S. Pym, Thierry Garnier and Stewart T. Cole


On direct comparison of minimal sets of ordered clones from bacterial artificial chromosome (BAC) libraries representing the complete genomes of Mycobacterium tuberculosis H37Rv and the vaccine strain, Mycobacterium bovis BCG Pasteur, two major rearrangements were identified in the genome of M. bovis BCG Pasteur. These were shown to correspond to two tandem duplications, DU1 and DU2, of 29 668 bp and 36 161 bp, respectively. While DU1 resulted from a single duplication event, DU2 apparently arose from duplication of a 100 kb genomic segment that subsequently incurred an internal deletion of 64 kb. Several lines of evidence suggest that DU2 may continue to expand, since two copies were detected in a subpopulation of BCG Pasteur cells. BCG strains harbouring DU1 and DU2 are diploid for at least 58 genes and contain two copies of oriC, the chromosomal origin of replication. These findings indicate that these genomic regions of the BCG genome are still dynamic. Although the role of DU1 and DU2 in the attenuation and/or altered immunogenicity of BCG is yet unknown, knowledge of their existence will facilitate quality control of BCG vaccine lots and may help in monitoring the efficacy of the world's most widely used vaccine

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:2448323
Provided by: PubMed Central
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    1. (1999). A historical and molecular phylogeny of BCG strains. Vaccine
    2. (1998). an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2).
    3. (1999). Analysis of the proteome of Mycobacterium tuberculosis in vitro. Tubercul Lung Dis
    4. (1999). Characterization of the functional replication origin of Mycobacterium tuberculosis. Gene
    5. (1996). Chromosomal duplications in bacteria, fruit ¯ies, and humans.
    6. (1996). Cole ST. An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.
    7. (1996). Comparison of immune responses of mice immunized with ®ve different Mycobacterium bovis BCG vaccine strains. Infect Immun
    8. (1997). Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis.
    9. (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature
    10. (1999). Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree. Tubercul Lung Dis
    11. (1995). Genetic differences between BCG substrains. Tubercul Lung Dis
    12. (1999). Genomic analysis reveals variation between Mycobacterium tuberculosis H37Rv and the attenuated M. tuberculosis H37Ra. Infect Immun
    13. (1999). Identi®cation of variable regions in the genomes of tubercle bacilli using bacterial arti®cial chromosome arrays. Mol Microbiol
    14. (1997). Increased intracellular survival of Mycobacterium smegmatis containing the Mycobacterium leprae thioredoxin-thioredoxin reductase gene. Infect Immun
    15. (1990). IS6110, an IS-like element of Mycobacterium tuberculosis.
    16. La Vaccination Contre la Tuberculose.
    17. (1996). Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent
    18. (1999). New insertion sequences and a novel repeated sequence in the genome of Mycobacterium tuberculosis H37Rv. Microbiology
    19. (1996). Organization of the origins of replication of the chromosomes of M. smegmatis, M. leprae and Mycobacterium tuberculosis and isolation of a functional origin from M. smegmatis. Mol Microbiol
    20. (1996). Physical mapping of Mycobacterium bovis BCG Pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from Mycobacterium bovis.
    21. (2000). Pulsed-®eld ®ngerprinting of listeriae: identi®cation of two genomic divisions for L. 122 R. Brosch et al. Copyright #
    22. (1981). Recombination between short DNA homologies causes tandem duplication.
    23. The BCG experience: implications for future vaccines against tuberculosis.
    24. (1998). Use of a Mycobacterium tuberculosis H37Rv bacterial arti®cial chromosome (BAC) library for genome mapping, sequencing and comparative genomics. Infect Immun
    25. (1995). Variation in protection by BCG: implications of and for heterologous immunity. Lancet

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