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 Behr, M. A.
Right arrow Articles by Barry, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Behr, M. A.
Right arrow Articles by Barry, C. E., III

 Previous Article  |  Next Article 

Journal of Bacteriology, June 2000, p. 3394-3399, Vol. 182, No. 12
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Point Mutation in the mma3 Gene Is Responsible for Impaired Methoxymycolic Acid Production in Mycobacterium bovis BCG Strains Obtained after 1927

Marcel A. Behr,1,* Benjamin G. Schroeder,2 Jacquelyn N. Brinkman,1 Richard A. Slayden,2 and Clifton E. Barry III2

McGill University Health Centre, Montreal, Canada H3G 1A4,1 and Tuberculosis Research Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 208522

Received 12 January 2000/Accepted 29 March 2000

BCG vaccines are substrains of Mycobacterium bovis derived by attenuation in vitro. After the original attenuation (1908 to 1921), BCG strains were maintained by serial propagation in different BCG laboratories (1921 to 1961). As a result, various BCG substrains developed which are now known to differ in a number of genetic and phenotypic properties. However, to date, none of these differences has permitted a direct phenotype-genotype link. Since BCG strains differ in their abilities to synthesize methoxymycolic acids and since recent work has shown that the mma3 gene is responsible for O-methylation of hydroxymycolate precursors to form methoxymycolic acids, we analyzed methoxymycolate production and mma3 gene sequences for a genetically defined collection of BCG strains. We found that BCG strains obtained from the Pasteur Institute in 1927 and earlier produced methoxymycolates in vitro but that those obtained from the Pasteur Institute in 1931 and later all failed to synthesize methoxymycolates, and furthermore, the mma3 sequence of the latter strains differs from that of Mycobacterium tuberculosis H37Rv by a point mutation at bp 293. Site-specific introduction of this guanine-to-adenine mutation into wild-type mma3 (resulting in the replacement of glycine 98 with aspartic acid) eliminated the ability of this enzyme to produce O-methylated mycolic acids when the mutant was cloned in tandem with mma4 into Mycobacterium smegmatis. These findings indicate that a point mutation in mma3 occurred between 1927 and 1931, and that this mutant population became the dominant clone of BCG at the Pasteur Institute.

* Corresponding author. Mailing address: A5-156, Montreal General Hospital, 1650 Cedar Ave., Montreal, Canada, H3G 1A4. Phone: (514) 937-6011, ext. 2815. Fax: (514) 934-8016. E-mail: mbgq{at}musica.mcgill.ca.

Journal of Bacteriology, June 2000, p. 3394-3399, Vol. 182, No. 12
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Garcia Pelayo, M. C., Uplekar, S., Keniry, A., Mendoza Lopez, P., Garnier, T., Nunez Garcia, J., Boschiroli, L., Zhou, X., Parkhill, J., Smith, N., Hewinson, R. G., Cole, S. T., Gordon, S. V. (2009). A Comprehensive Survey of Single Nucleotide Polymorphisms (SNPs) across Mycobacterium bovis Strains and M. bovis BCG Vaccine Strains Refines the Genealogy and Defines a Minimal Set of SNPs That Separate Virulent M. bovis Strains and M. bovis BCG Strains. Infect. Immun. 77: 2230-2238 [Abstract] [Full Text]  
  • Mackenzie, N., Alexander, D. C., Turenne, C. Y., Behr, M. A., De Buck, J. M. (2009). Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex. J. Clin. Microbiol. 47: 1002-1011 [Abstract] [Full Text]  
  • Wheeler, P. R., Brosch, R., Coldham, N. G., Inwald, J. K., Hewinson, R. G., Gordon, S. V. (2008). Functional analysis of a clonal deletion in an epidemic strain of Mycobacterium bovis reveals a role in lipid metabolism. Microbiology 154: 3731-3742 [Abstract] [Full Text]  
  • Griffiths, T. A., Rioux, K., De Buck, J. (2008). Sequence Polymorphisms in a Surface PPE Protein Distinguish Types I, II, and III of Mycobacterium avium subsp. paratuberculosis. J. Clin. Microbiol. 46: 1207-1212 [Abstract] [Full Text]  
  • Dover, L. G., Alahari, A., Gratraud, P., Gomes, J. M., Bhowruth, V., Reynolds, R. C., Besra, G. S., Kremer, L. (2007). EthA, a Common Activator of Thiocarbamide-Containing Drugs Acting on Different Mycobacterial Targets. Antimicrob. Agents Chemother. 51: 1055-1063 [Abstract] [Full Text]  
  • Boissier, F., Bardou, F., Guillet, V., Uttenweiler-Joseph, S., Daffe, M., Quemard, A., Mourey, L. (2006). Further Insight into S-Adenosylmethionine-dependent Methyltransferases: STRUCTURAL CHARACTERIZATION OF Hma, AN ENZYME ESSENTIAL FOR THE BIOSYNTHESIS OF OXYGENATED MYCOLIC ACIDS IN MYCOBACTERIUM TUBERCULOSIS. J. Biol. Chem. 281: 4434-4445 [Abstract] [Full Text]  
  • Spreadbury, C. L., Pallen, M. J., Overton, T., Behr, M. A., Mostowy, S., Spiro, S., Busby, S. J. W., Cole, J. A. (2005). Point mutations in the DNA- and cNMP-binding domains of the homologue of the cAMP receptor protein (CRP) in Mycobacterium bovis BCG: implications for the inactivation of a global regulator and strain attenuation. Microbiology 151: 547-556 [Abstract] [Full Text]  
  • Belley, A., Alexander, D., Di Pietrantonio, T., Girard, M., Jones, J., Schurr, E., Liu, J., Sherman, D. R., Behr, M. A. (2004). Impact of Methoxymycolic Acid Production by Mycobacterium bovis BCG Vaccines. Infect. Immun. 72: 2803-2809 [Abstract] [Full Text]  
  • Dinadayala, P., Lemassu, A., Granovski, P., Cerantola, S., Winter, N., Daffe, M. (2004). Revisiting the Structure of the Anti-neoplastic Glucans of Mycobacterium bovis Bacille Calmette-Guerin: STRUCTURAL ANALYSIS OF THE EXTRACELLULAR AND BOILING WATER EXTRACT-DERIVED GLUCANS OF THE VACCINE SUBSTRAINS. J. Biol. Chem. 279: 12369-12378 [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»