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A recA deletion mutant of Mycobacterium bovis BCG confers protection equivalent to that of wild-type BCG but shows increased genetic stability


Sander, P; Böttger, E C; Springer, B; Steinmann, B; Rezwan, M; Stavropoulos, E; Colston, M J (2003). A recA deletion mutant of Mycobacterium bovis BCG confers protection equivalent to that of wild-type BCG but shows increased genetic stability. Vaccine, 21(27-30):4124-4127.

Abstract

The widely used vaccine against tuberculosis, BCG, shows evidence of genetic instability. It has undergone major genetic rearrangements resulting in deletion and duplication of segments of its chromosome. In order to produce a BCG strain with more favourable genetic properties, we inactivated the recA gene. Targeted deletion of the recA gene of BCG resulted in a complete loss of recombination between homologous, chromosomally-located sequences, as well as between plasmid- and chromosomally-located sequences. The deltarecA mutant BCG was as effective as the wild-type in conferring protection in mice against an intravenous challenge with virulent Mycobacterium tuberculosis, indicating that the loss of an SOS response-mediated DNA repair mechanism did not compromise the immunological properties of BCG. The availability of a genetically stable, fully immunogenic BCG is important for the future development of BCG as a live vaccine.

The widely used vaccine against tuberculosis, BCG, shows evidence of genetic instability. It has undergone major genetic rearrangements resulting in deletion and duplication of segments of its chromosome. In order to produce a BCG strain with more favourable genetic properties, we inactivated the recA gene. Targeted deletion of the recA gene of BCG resulted in a complete loss of recombination between homologous, chromosomally-located sequences, as well as between plasmid- and chromosomally-located sequences. The deltarecA mutant BCG was as effective as the wild-type in conferring protection in mice against an intravenous challenge with virulent Mycobacterium tuberculosis, indicating that the loss of an SOS response-mediated DNA repair mechanism did not compromise the immunological properties of BCG. The availability of a genetically stable, fully immunogenic BCG is important for the future development of BCG as a live vaccine.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:October 2003
Deposited On:22 Aug 2008 12:12
Last Modified:05 Apr 2016 12:26
Publisher:Elsevier
ISSN:0264-410X
Publisher DOI:10.1016/S0264-410X(03)00434-1
PubMed ID:14505891
Permanent URL: http://doi.org/10.5167/uzh-3255

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