Comparative Genomics and Evolution of Mycobacterium bovis BCG

Roland Brosch; Marcel A. Behr

doi:10.1128/9781555817657.ch10

Chapter 10 : Comparative Genomics and Evolution of Mycobacterium bovis BCG

Authors: Roland Brosch¹, Marcel A. Behr²

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Affiliations: 1: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France; 2: Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, A5-156, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC H3G 1A4 Canada

Content Type: Monograph

Publication Year: 2005

Category: Bacterial Pathogenesis; Clinical Microbiology

Book DOI: 10.1128/9781555817657

Chapter DOI: 10.1128/9781555817657.ch10

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Abstract:

Recent advances in the field of mycobacterial genetics, genomics, comparative genomics, and related techniques have supplied an enormous amount of new information, which is summarized and discussed in this chapter. Lyophilization of vaccine lots became available in the latter half of the 20th century, exposing different BCG daughter strains to some 1,000 additional passages of in vitro evolution in different laboratories. Specific PCR and sequence analyses of these RD regions, among members of the Mycobacterium tuberculosis complex, showed that most of the RD regions absent from BCG were also missing from other strains of Mycobacterium bovis, indicating that some of these variable regions reflect the evolutionary divergence of M. tuberculosis and M. bovis rather than being genomic modifications that were introduced during the attenuation process of BCG. Using the historical records about when and where BCG strains were distributed, together with information about genetic particularities of certain BCG substrains, reconstruction of the short-term evolution of BCG strains can be established. With prototype sequence information, along with comparative genomic tools such as subtractive hybridization, bacterial artificial chromosome (BAC) libraries, and DNA microarrays, the discovery of genomic deletions has been greatly facilitated. The situation in mycobacterial research has considerably changed in the last few years due to the information contained in the whole-genome sequence of M. tuberculosis H37Rv. A more efficient anti-TB vaccine seems to be one of the few possible public health interventions that would really have a major impact on the improvement of the worldwide TB situation.

Citation: Brosch R, Behr M. 2005. Comparative Genomics and Evolution of Mycobacterium bovis BCG, p 155-164. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch10

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Comparative Genomics and Evolution of Mycobacterium bovis BCG

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Figure 1.

BCG genealogy. The vertical axis represents time, and the horizontal axis represents movement of vaccines between laboratories. Solid lines indicate deletions, and the dotted line indicates an SNP in mmaA3.

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Figure 1.

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Figure 2

Comparison of the genomic region RD9 from M. tuberculosis H37Rv and M. bovis. A 2-kb fragment including highly conserved parts of cobL is absent from BCG, M. bovis, M. microti, and M. africanum strains but is present in M. tuberculosis and M. canetti.

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Figure 2

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Figure 3

Evolutionary scheme of the M. tuberculosis complex, indicating that M. bovis BCG has lost numerous regions of difference, several of which are in common with other strains of the complex. Adapted from reference 10 with permission.

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Figure 3

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Tables

Comparative Genomics and Evolution of Mycobacterium bovis BCG

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Table 1

Genomic deletions in certain BCG substrains

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Table 1

Genomic deletions in certain BCG substrains