ArticleInfection and immunity2003
Mycobacterium bovis BCG vaccines exhibit defects in alanine and serine catabolism.
Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- Dopamine alters macrophage metabolism promoting intracellular Mycobacterium tuberculosis survival.Molecular medicine (Cambridge, Mass.) · 2026Article
- Characterizing the immune response toFrontiers in immunology · 2024Review
- Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines.Frontiers in immunology · 2023Article
- Metabolomic changes in Mycobacterium avium subsp. paratuberculosis (MAP) challenged Holstein-Friesian cattle highlight the role of serum amino acids as indicators of immune system activation.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Each Mycobacterium Requires a Specific Culture Medium Composition for Triggering an Optimized Immunomodulatory and Antitumoral Effect.Microorganisms · 2020Article
- BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny.Frontiers in microbiology · 2020Review
- The prominent alteration in transcriptome and metabolome of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin BBMC microbiology · 2019Article
- Alanine dehydrogenases in mycobacteria.Journal of microbiology (Seoul, Korea) · 2019Review
- Roles of Alanine Dehydrogenase and Induction of Its Gene in Mycobacterium smegmatis under Respiration-Inhibitory Conditions.Journal of bacteriology · 2018Article
- Enhanced survival of BCG-stimulated dendritic cells: involvement of anti-apoptotic proteins and NF-κB.Biology open · 2018Article
- Crucial requirement for standardization during the development of novel recombinant BCG vaccines: Does the corresponding substrain background matter?Human vaccines & immunotherapeutics · 2016Article
- Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.Nature genetics · 2016Article
- Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence.PloS one · 2016Article
- The Mycobacterium tuberculosis H37Ra gene MRA_1916 causes growth defects upon down-regulation.Scientific reports · 2015Article
- Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR.Journal of bacteriology · 2015Article
- Structure of L-serine dehydratase from Legionella pneumophila: novel use of the C-terminal cysteine as an intrinsic competitive inhibitor.Biochemistry · 2014Article
- Regulation of the ald gene encoding alanine dehydrogenase by AldR in Mycobacterium smegmatis.Journal of bacteriology · 2013Article
- The role of glutamine oxoglutarate aminotransferase and glutamate dehydrogenase in nitrogen metabolism in Mycobacterium bovis BCG.PloS one · 2013Article
- Systems-based approaches to probing metabolic variation within the Mycobacterium tuberculosis complex.PloS one · 2013Article
- ald of Mycobacterium tuberculosis encodes both the alanine dehydrogenase and the putative glycine dehydrogenase.Journal of bacteriology · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.