ArticleThe Journal of biological chemistry2008
Biosynthesis and recycling of nicotinamide cofactors in mycobacterium tuberculosis. An essential role for NAD in nonreplicating bacilli.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates.Antimicrobial agents and chemotherapy · 2015Pooled it
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells.PloS one · 2026Article
- Exploring the Protein Landscape of Dormant Mycobacterium tuberculosis Through In Vitro Functional Studies.Advances in experimental medicine and biology · 2026Review
- Mycobacterium tuberculosis biology, pathogenicity and interaction with the host.Nature reviews. Microbiology · 2025Review
- Essential redundancies fuel Mycobacterium tuberculosis adaptation to the host.PLoS pathogens · 2025Review
- In silico studies on nicotinamide analogs as competitive inhibitors of nicotinamidase in methicillin-resistant Staphylococcus aureus.Molecular diversity · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- Disruptive DNA Intercalation Is the Mode of Interaction Behind Niacinamide Antimicrobial Activity.Microorganisms · 2025Article
- Oxidative stress drives potent bactericidal activity of pyrazinamide againstbioRxiv : the preprint server for biology · 2024Article
- Niacinamide Antimicrobial Efficacy and Its Mode of Action via Microbial Cell Cycle Arrest.Microorganisms · 2024Article
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- Transposon sequencing reveals metabolic pathways essential for Mycobacterium tuberculosis infection.PLoS pathogens · 2024Article
- Exposure ofFrontiers in tuberculosis · 2024Article
- Harnessing redox proteomics to study metabolic regulation and stress response in lignin-fed Rhodococci.Biotechnology for biofuels and bioproducts · 2023Article
- NADNature communications · 2023Article
- Article
- Article
- Molecular Connectivity between Extracytoplasmic Sigma Factors and PhoP Accounts for Coupled Mycobacterial Stress Response.Journal of bacteriology · 2022Article
- Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition.Cell reports · 2022Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Despite the presence of genes that apparently encode NAD salvage-specific enzymes in its genome, it has been previously thought that Mycobacterium tuberculosis can only synthesize NAD de novo. Transcriptional analysis of the de novo synthesis and putative salvage pathway genes revealed an up-regulation of the salvage pathway genes in vivo and in vitro under conditions of hypoxia. [14C]Nicotinamide incorporation assays in M. tuberculosis isolated directly from the lungs of infected mice or from infected macrophages revealed that incorporation of exogenous nicotinamide was very efficient in in vivo-adapted cells, in contrast to cells grown aerobically in vitro. Two putative nicotinic acid phosphoribosyltransferases, PncB1 (Rv1330c) and PncB2 (Rv0573c), were examined by a combination of in vitro enzymatic activity assays and allelic exchange studies. These studies revealed that both play a role in cofactor salvage. Mutants in the de novo pathway died upon removal of exogenous nicotinamide during active replication in vitro. Cell death is induced by both cofactor starvation and disruption of cellular redox homeostasis as electron transport is impaired by limiting NAD. Inhibitors of NAD synthetase, an essential enzyme common to both recycling and de novo synthesis pathways, displayed the same bactericidal effect as sudden NAD starvation of the de novo pathway mutant in both actively growing and nonreplicating M. tuberculosis. These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis.
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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.