ArticleJournal of bacteriology2013
Quinolinate salvage and insights for targeting NAD biosynthesis in group A streptococci.
Article in Journal of bacteriology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Nutrient control enables metabolic reconstruction ofbioRxiv : the preprint server for biology · 2026Article
- In silico studies on nicotinamide analogs as competitive inhibitors of nicotinamidase in methicillin-resistant Staphylococcus aureus.Molecular diversity · 2025Article
- Periplasmic binding proteins Bug69 and Bug27 from Bordetella pertussis are in vitro high-affinity quinolinate binders with a potential role in NAD biosynthesis.FEBS open bio · 2024Article
- Symbiosis of Carpenter Bees with Uncharacterized Lactic Acid Bacteria Showing NAD Auxotrophy.Microbiology spectrum · 2023Article
- Article
- Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition.Cell reports · 2022Article
- The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors.Frontiers in microbiology · 2020Review
- Novel Antimycobacterial Compounds Suppress NAD Biogenesis by Targeting a Unique Pocket of NaMN Adenylyltransferase.ACS chemical biology · 2019Article
- Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome.Frontiers in microbiology · 2019Article
- Article
- A Key Enzyme of the NADJournal of bacteriology · 2017Article
- Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NHThe FEBS journal · 2017Article
- Biological Activities of the Essential Oil from Erigeron floribundus.Molecules (Basel, Switzerland) · 2016Article
- Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.The Journal of nutrition · 2016Article
- Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae.Microbiology (Reading, England) · 2015Article
- Mycobacterial nicotinate mononucleotide adenylyltransferase: structure, mechanism, and implications for drug discovery.The Journal of biological chemistry · 2015Article
- Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis.Frontiers in molecular biosciences · 2015Review
- Cytosine chemoreceptor McpC in Pseudomonas putida F1 also detects nicotinic acid.Microbiology (Reading, England) · 2014Article
- Metabolic and bactericidal effects of targeted suppression of NadD and NadE enzymes in mycobacteria.mBio · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The essential coenzyme NAD plays important roles in metabolic reactions and cell regulation in all organisms. As such, NAD synthesis has been investigated as a source for novel antibacterial targets. Cross-species genomics-based reconstructions of NAD metabolism in group A streptococci (GAS), combined with focused experimental testing in Streptococcus pyogenes, led to a better understanding of NAD metabolism in the pathogen. The predicted niacin auxotrophy was experimentally verified, as well as the essential role of the nicotinamidase PncA in the utilization of nicotinamide (Nm). PncA is dispensable in the presence of nicotinate (Na), ruling it out as a viable antibacterial target. The function of the "orphan" NadC enzyme, which is uniquely present in all GAS species despite the absence of other genes of NAD de novo synthesis, was elucidated. Indeed, the quinolinate (Qa) phosphoribosyltransferase activity of NadC from S. pyogenes allows the organism to sustain growth when Qa is present as a sole pyridine precursor. Finally, the redundancy of functional upstream salvage pathways in GAS species narrows the choice of potential drug targets to the two indispensable downstream enzymes of NAD synthesis, nicotinate adenylyltransferase (NadD family) and NAD synthetase (NadE family). Biochemical characterization of NadD confirmed its functional role in S. pyogenes, and its potential as an antibacterial target was supported by inhibition studies with previously identified class I inhibitors of the NadD enzyme family. One of these inhibitors efficiently inhibited S. pyogenes NadD (sp.NadD) in vitro (50% inhibitory concentration [IC(50)], 15 μM), exhibiting a noncompetitive mechanism with a K(i) of 8 μM.
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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.