Skip to main content
SpringerLink
Log in

Genomics of the Mycobacterium tuberculosis Complex and BCG Vaccines

  • Chapter
Pathogen Genomics

Part of the book series: Infectious Disease ((ID))

  • 120 Accesses

Abstract

Despite the existence of the M. bovis bacillus Calmette-Guerin (BCG) vaccine since the 1920’s (BCG) and the availability of effective antimicrobial therapy since the 1950s, tuberculosis (TB) remains a pathogen of major importance. Current estimates indicate that one-third of the world’s population is infected by M. tuberculosis with an estimated 8 million new cases and 1.9 million deaths attributable to tuberculosis each year (1). Although antimicrobial therapy should theoretically convert this deadly disease into a treatable bacterial infection, programmatic limitations prevent many of the victims from obtaining effective therapy. In regions where drugs have been available, inappropriate use has led to the selection of drug-resistant bacilli (2). Furthermore, the synergy between HIV/AIDS and TB and the added difficulties of treating both these diseases with complex multi-drug cocktails suggest that control of TB with antimicrobial agents alone may remain an elusive challenge. This paucity of chemotherapeutic options is compounded by the variable efficacy of the live attenuated M. bovis BCG vaccine strains in clinical settings (3).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282 (7): 677–686.

    Article  PubMed  CAS  Google Scholar 

  2. Espinal MA, Laszlo A, Simonsen L, Boulahbal F, Kim SJ, Reniero A, et al. Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med 2001; 344 (17): 1294–1303.

    Article  PubMed  CAS  Google Scholar 

  3. Fine PE. Bacille Calmette-Guerin vaccines: a rough guide. Clin Infect Dis 1995; 20 (1): 11–14.

    Article  PubMed  CAS  Google Scholar 

  4. Calmette A, Guérin C. Recherches expérimentales sur la défense de l’organisme contre l’infection tuberculeuse. Ann Inst Pasteur 1911; 25: 625–641.

    Google Scholar 

  5. Lowrie DB, Tascon RE, Bonato VL, Lima VM, Faccioli LH, Stavropoulos E, et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 1999; 400 (6741): 269–271.

    Article  PubMed  CAS  Google Scholar 

  6. Vidal SM, Malo D, Vogan K, Skamene E, Gros R. Natural resistance to infection with intracellular parasites: isolation of a candidate for BCG. Cell 1993; 73 (3): 469–485.

    Article  PubMed  CAS  Google Scholar 

  7. Greenwood CM, Fujiwara TM, Boothroyd LJ, Miller MA, Frappier D, Fanning EA, et al. Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family Am J Hum Genet 2000; 67 (2): 405–416.

    CAS  Google Scholar 

  8. Cole ST, Brosch R, Parkhill J, Gamier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;11;393(6685):537–544.

    Google Scholar 

  9. http://www.tigr.org/tigr-scripts/CMR2/GenomePage3.spl?database=gmt

    Google Scholar 

  10. Grange JM, Gibson J, Osborn TW, Collins CH, Yates MD. What is BCG? Tubercle 1983; 64 (2): 129–139.

    Article  CAS  Google Scholar 

  11. Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, et al. Massive gene decay in the leprosy bacillus. Nature 2001;22;409(6823):1007–1011.

    Google Scholar 

  12. Sreevatsan S, Pan X, Stockbauer KE, Connell ND, Kreiswirth BN, Whittam TS, et al. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc Natl Acad Sci USA 1997; 94 (18): 9869–9874.

    Article  PubMed  CAS  Google Scholar 

  13. Fraser CM, Eisen J, Fleischmann RD, Ketchum KA, Peterson S. Comparative genomics and understanding of microbial biology. Emerg Infect Dis 2000; 6 (5): 505–512.

    Article  PubMed  CAS  Google Scholar 

  14. Brosch R, Philipp WJ, Stavropoulos E, Colston MJ, Cole ST, Gordon SV. Genomic analysis reveals variation between Mycobacterium tuberculosis H37Rv and the attenuated M. tuberculosis H37Ra strain. Infect Immun 1999; 67 (11): 5768–5774.

    PubMed  CAS  Google Scholar 

  15. Ho TB, Robertson BD, Taylor GM, Shaw RJ, Young DB. Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates. Yeast 2000; 17 (4): 272–282.

    Article  PubMed  CAS  Google Scholar 

  16. Kato-Maeda M, Rhee JT, Gingeras TR, Salamon H, Drenkow J, Smittipat N, et al. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res 2001; 11 (4): 547–554.

    Article  PubMed  CAS  Google Scholar 

  17. Salamon H, Kato-Maeda M, Small PM, Drenkow J, Gingeras TR. Detection of deleted genomic DNA using a semiautomated computational analysis of GeneChip data. Genome Res 2000; 10 (12): 2044–2054.

    Article  PubMed  CAS  Google Scholar 

  18. Betts JC, Dodson P, Quan S, Lewis AP, Thomas PI, Duncan K, et al. Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551. Microbiology 2000;146 Pt 12: 3205–3216.

    Google Scholar 

  19. Gordon SV, Brosch R, Billault A, Gamier T, Eiglmeier K, Cole ST. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol Microbiol 1999; 32 (3): 643–655.

    Article  PubMed  CAS  Google Scholar 

  20. Hewinson RG, Michell SL, Russell WP, McAdam RA, Jacobs WR Jr. Molecular characterization of MPT83: a seroreactive antigen of Mycobacterium tuberculosis with homology to MPT70. Scand J Immunol 1996; 43 (5): 490–499.

    Article  PubMed  CAS  Google Scholar 

  21. Hart PD, Sutherland I. BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Br Med J 1977; 2 (6082): 293–295.

    Article  PubMed  CAS  Google Scholar 

  22. Oettinger T, Jorgensen M, Ladefoged A, Haslov K, Andersen P. Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree. Tubercle Lung Dis 1999; 79 (4): 243–250.

    Article  CAS  Google Scholar 

  23. Behr MA, Small PM. A historical and molecular phylogeny of BCCi strains. Vaccine 1999 Feb 26; 17 (7–8): 915–922.

    CAS  Google Scholar 

  24. Casanova JL, Blanche S, Emile JF, Jouanguy E, Lamhamedi S, Altare F, et al. Idiopathic disseminated bacillus Calmette-Guerin infection: a French national retrospective study. Pediatrics 1996; 98 (4 Pt 1): 774–778.

    PubMed  CAS  Google Scholar 

  25. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and military tuberculosis: a meta-analysis. Int J Epidemiol 1993; 22 (6): 1154–1158.

    Article  PubMed  CAS  Google Scholar 

  26. Fomukong NG, Dale JW, Osborn TW, Grange JM. Use of gene probes based on the insertion sequence IS986 to differentiate between BCG vaccine strains. J Appl Bacteriol 1992; 72 (2): 126–133.

    Article  PubMed  CAS  Google Scholar 

  27. Li H, Ulstrup JC, Jonassen TO, Melby K, Nagai S, Harboe M. Evidence for absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG. Infect Immun 1993; 61 (5): 1730–1734.

    PubMed  CAS  Google Scholar 

  28. Yuan Y, Zhu Y, Crane DD, Barry CE, 3rd. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol Microbiol 1998; 29 (6): 1449–1458.

    Article  PubMed  CAS  Google Scholar 

  29. Mahairas GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol 1996; 178 (5): 1274–1282.

    PubMed  CAS  Google Scholar 

  30. Brosch R, Gordon SV, Buchrieser C, Pym AS, Gamier T, Cole ST. Comparative genomics uncovers large tandem chromosomal duplications in Mycobacterium bovis BCG Pasteur. Yeast 2000;30;17(2):111–123.

    Google Scholar 

  31. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 1999; 284 (5419): 1520–1523.

    Article  Google Scholar 

  32. Jungblut PR, Schaible UE, Mollenkopf HJ, Zimny-Arndt U, Raupach B, Mattow J, et al. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol Microbiol 1999;(6):1103–1117.

    Google Scholar 

  33. Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic’ S. Recombinant bacillus calmetteguerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc Natl Acad Sci USA 2000;97(25):13,853–13,858.

    Google Scholar 

Download references

Authors
  1. Marcel A. Behr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen V. Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Infectious Diseases, Johnson and Johnson Pharmaceutical Research and Development, L. L. C., San Diego, CA, USA

    Karen Joy Shaw PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Behr, M.A., Gordon, S.V. (2002). Genomics of the Mycobacterium tuberculosis Complex and BCG Vaccines. In: Shaw, K.J. (eds) Pathogen Genomics. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-172-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-172-5_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9683-3

  • Online ISBN: 978-1-59259-172-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation