Physical mapping of Mycobacterium bovis BCG Pasteur reveals differences from the genome maps of Mycobacterium tuberculosis H37Rv and M. bovis

Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France.
Microbiology (Impact Factor: 2.56). 12/1996; 142 ( Pt 11)(11):3135-45. DOI: 10.1099/13500872-142-11-3135
Source: PubMed


A Dral restriction map of the approximately 4.35 Mb circular chromosome of the vaccine strain Mycobacterium bovis BCG Pasteur was constructed by linking all 21 Dral fragments, ranging in size from 6 to 820 kb, using specific clones that spanned the Dral recognition sites as hybridization probes. The positions of 20 known genes were also established. Comparison of the resultant genome map with that of the virulent tubercle bacillus Mycobacterium tuberculosis H37Rv revealed extensive global conservation of the genomes of these two members of the M. tuberculosis complex. Possible sites of evolutionary rearrangements were localized on the chromosome of M. bovis BCG Pasteur by comparing the Asnl restriction profile with that of M. tuberculosis H37Rv. When selected cosmids from the corresponding areas of the genome of M. tuberculosis H37Rv were used as hybridization probes to examine different BCG strains, wild-type M. bovis and M. tuberculosis H37Rv, a number of deletions up to 10 kb in size, insertions and other polymorphisms were detected. In addition to the known deletions covering the genes for the protein antigens ESAT-6 and mpt64, other genetic loci exhibiting polymorphisms or rearrangements were detected in M. bovis BCG Pasteur.

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Available from: W. Philipp, Jan 27, 2014
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    • "Avirulent BCG was produced after 230 serial passages of M. bovis and it is utilized to prevent extensive forms of tuberculosis. The mechanisms involved in its avirulence were obscure until recently when by sequencing the complete BCG chromosome, deletions of DNA stretches of up to 10-kb (designated as RD, regions of difference) were observed [7]. The reconstitution of some of these genes restores most of the virulence of M. bovis BCG [8]. "
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    • "Here, we used optical mapping [11] to examine genomic rearrangements between M. ap K-10, the recently sequenced strain, and ATCC 19698, the type strain of M. ap. Physical mapping has been conducted to compare genomes between M. tuberculosis and M. bovis [19] and between M. tuberculosis and M. leprae [20]. By taking the advantages of current technology, we are able to generate a high-resolution physical map of M. ap. "
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    • "Over the past decade, numerous groups have sought to identify the genomic changes responsible for these phenotypes. The earliest whole genome comparisons confirmed that BCG was indeed related to, but distinct from M. tb and M. bovis [17-19]. Subsequent analyses of multiple vaccine strains have uncovered extensive genome diversity including both deletions and duplications in BCG substrains [18,20-22]. "
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