Mycobacterium bovis BCG Vaccines Exhibit Defects in Alanine and Serine Catabolism
AUTOR(ES)
Chen, Jeffrey M.
FONTE
American Society for Microbiology
RESUMO
Mycobacterium bovis BCG is the only accepted vaccine for the prevention of tuberculosis (TB) in humans. BCG is a live vaccine, and induction of immunity to TB requires productive infection of the host by BCG. However, BCG is not a satisfactory vaccine, because it fails to protect against pulmonary TB in adults. In this study, we found that BCG strains cannot utilize many naturally occurring amino acids as the sole nitrogen source for growth. This defect is caused, at least partially, by the lack of functional metabolic enzymes. All BCG strains are unable to catabolize l-alanine or d-alanine due to a frameshift mutation in the l-alanine dehydrogenase gene (ald). Some BCG strains, such as BCG-Pasteur and BCG-Frappier, cannot catabolize l-serine, apparently due to inadequate expression of l-serine deaminase (sdaA). We also found that undegraded alanine and serine inhibit the growth of BCG through blockage of glutamine synthetase. These results suggest that BCG strains are limited in nitrogen metabolic capacity and predict defects that may restrict multiplication and persistence of the live vaccine within the host.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=145370Documentos Relacionados
- Impact of Methoxymycolic Acid Production by Mycobacterium bovis BCG Vaccines
- Characterization of Mycobacterium bovis BCG vaccines by DNA fingerprinting by a standardized methodology.
- PCR identification of Mycobacterium bovis BCG.
- Oxygen Depletion-Induced Dormancy in Mycobacterium bovis BCG
- Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene.