This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sander, P.
Right arrow Articles by Böttger, E. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sander, P.
Right arrow Articles by Böttger, E. C.

 Previous Article  |  Next Article 

Infection and Immunity, June 2001, p. 3562-3568, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3562-3568.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mycobacterium bovis BCG recA Deletion Mutant Shows Increased Susceptibility to DNA-Damaging Agents but Wild-Type Survival in a Mouse Infection Model

Peter Sander,1,2,* K. G. Papavinasasundaram,2 Thomas Dick,3 Evangelos Stavropoulos,2 Kerstin Ellrott,1 Burkhard Springer,1 M. Joseph Colston,2 and Erik C. Böttger1,4

Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany1; National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom2; Institute of Molecular and Cell Biology, Singapore 117609, Republic of Singapore3; and Institut für Medizinische Mikrobiologie, Universität Zürich, 8028 Zürich, Switzerland4

Received 20 October 2000/Returned for modification 28 December 2000/Accepted 26 February 2001

Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxifies reactive oxygen species, and DNA repair systems, which repair damage resulting from oxidative stress. To (i) determine the relative importance of the DNA repair system when oxidative stress is encountered by the Mycobacterium tuberculosis complex during infection of the host and to (ii) provide improved mycobacterial hosts as live carriers to express foreign antigens, the recA locus was inactivated by allelic exchange in Mycobacterium bovis BCG. The recA mutants are sensitive to DNA-damaging agents and show increased susceptibility to metronidazole, the first lead compound active against the dormant M. tuberculosis complex. Surprisingly, the recA genotype does not affect the in vitro dormancy response, nor does the defect in the DNA repair system lead to attenuation as determined in a mouse infection model. The recA mutants will be a valuable tool for further development of BCG as an antigen delivery system to express foreign antigens and as a source of a genetically stable vaccine against tuberculosis.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Phone: 511-532-4348. Fax: 511-532-4366. E-mail: Sander.peter{at}gmx.de.

Infection and Immunity, June 2001, p. 3562-3568, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3562-3568.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Stephanou, N. C., Gao, F., Bongiorno, P., Ehrt, S., Schnappinger, D., Shuman, S., Glickman, M. S. (2007). Mycobacterial Nonhomologous End Joining Mediates Mutagenic Repair of Chromosomal Double-Strand DNA Breaks. J. Bacteriol. 189: 5237-5246 [Abstract] [Full Text]  
  • Warner, D. F., Mizrahi, V. (2006). Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy. Clin. Microbiol. Rev. 19: 558-570 [Abstract] [Full Text]  
  • Huet, G., Daffe, M., Saves, I. (2005). Identification of the Mycobacterium tuberculosis SUF Machinery as the Exclusive Mycobacterial System of [Fe-S] Cluster Assembly: Evidence for Its Implication in the Pathogen's Survival. J. Bacteriol. 187: 6137-6146 [Abstract] [Full Text]  
  • Darwin, K. H., Nathan, C. F. (2005). Role for Nucleotide Excision Repair in Virulence of Mycobacterium tuberculosis. Infect. Immun. 73: 4581-4587 [Abstract] [Full Text]  
  • Frota, C. C., Papavinasasundaram, K. G., Davis, E. O., Colston, M. J. (2004). The AraC Family Transcriptional Regulator Rv1931c Plays a Role in the Virulence of Mycobacterium tuberculosis. Infect. Immun. 72: 5483-5486 [Abstract] [Full Text]  
  • Enanga, B., Ariyanayagam, M. R., Stewart, M. L., Barrett, M. P. (2003). Activity of Megazol, a Trypanocidal Nitroimidazole, Is Associated with DNA Damage. Antimicrob. Agents Chemother. 47: 3368-3370 [Abstract] [Full Text]  
  • Venkatesh, J., Kumar, P., Krishna, P. S. M., Manjunath, R., Varshney, U. (2003). Importance of Uracil DNA Glycosylase in Pseudomonas aeruginosa and Mycobacterium smegmatis, G+C-rich Bacteria, in Mutation Prevention, Tolerance to Acidified Nitrite, and Endurance in Mouse Macrophages. J. Biol. Chem. 278: 24350-24358 [Abstract] [Full Text]  
  • Durbach, S. I., Springer, B., Machowski, E. E., North, R. J., Papavinasasundaram, K. G., Colston, M. J., Bottger, E. C., Mizrahi, V. (2003). DNA Alkylation Damage as a Sensor of Nitrosative Stress in Mycobacterium tuberculosis. Infect. Immun. 71: 997-1000 [Abstract] [Full Text]  
  • Boon, C., Dick, T. (2002). Mycobacterium bovis BCG Response Regulator Essential for Hypoxic Dormancy. J. Bacteriol. 184: 6760-6767 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»