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Infection and Immunity, May 2004, p. 2803-2809, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2803-2809.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Impact of Methoxymycolic Acid Production by Mycobacterium bovis BCG Vaccines

Adam Belley,¹ David Alexander,² Tania Di Pietrantonio,¹ Manon Girard,¹ Joses Jones,² Erwin Schurr,¹ Jun Liu,² David R. Sherman,³ and Marcel A. Behr^1*

Centre for the Study of Host Resistance, McGill University, Montreal H3G 1A4,¹ Department of Medical Genetics and Microbiology, University of Toronto, Ontario M5S 1A8, Canada,² Department of Pathobiology, University of Washington, Seattle, Washington 98195³

Received 9 September 2003/ Returned for modification 4 December 2003/ Accepted 31 January 2004

BCG vaccines are a family of closely related daughter strains of an attenuated isolate of Mycobacterium bovis derived by in vitro passage from 1908 to 1921. During subsequent laboratory propagation of the vaccine strain until its lyophilization in 1961, BCG Pasteur underwent at least seven further genomic mutations. The impact of these mutations on the properties of the vaccine is currently unknown. One mutation, a glycine-to-aspartic acid substitution in the mmaA3 gene, occurred between 1927 and 1931 and impairs methoxymycolic acid synthesis in BCG strains obtained from the Pasteur Institute after this period. Mycolic acids of the cell wall are classified into three functional groups (alpha-, methoxy-, and ketomycolic acids), and together these lipids form a highly specialized permeability barrier around the bacterium. To explore the impact of methoxymycolic acid production by BCG strains, we complemented the functional gene of mmaA3 into BCG Denmark and tested a number of in vitro and in vivo phenotypes. Surprisingly, restoration of methoxymycolic acids alone had no effect on cell wall permeability, resistance to antibiotics, or growth in cultured macrophages and C57BL/6 mice. Our results demonstrate that the loss of methoxymycolic acid production did not apparently affect the virulence of BCG strains.

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* Corresponding author. Mailing address: Division of Infectious Diseases and Medical Microbiology, A5-156, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC, Canada. H3G 1A4. Phone: (514) 934-1934, x42815. Fax: (514) 934-8423. E-mail: marcel.behr{at}mcgill.ca.

Editor: V. J. DiRita

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Infection and Immunity, May 2004, p. 2803-2809, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2803-2809.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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