ArticleJournal of bacteriology2011
Dissecting complex metabolic integration provides direct genetic evidence for CodY activation by guanine nucleotides.
Article in Journal of bacteriology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- InJournal of bacteriology · 2026Article
- Naturally Occurring CodY Variants Alter Ligand Binding, DNA Target Affinity, and Virulence in Clostridioides difficile.Molecular microbiology · 2026Article
- InbioRxiv : the preprint server for biology · 2026Article
- Deciphering strain differences in codY regulation ofMicrobiology spectrum · 2026Article
- Disruption of purineFrontiers in microbiology · 2025Article
- CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis inJournal of bacteriology · 2024Article
- In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.Molecular microbiology · 2024Article
- Structural insights into CodY activation and DNA recognition.Nucleic acids research · 2023Article
- Regulation of the Sae Two-Component System by Branched-Chain Fatty Acids in Staphylococcus aureus.mBio · 2022Article
- Regulation of cid and lrg expression by CodY in Streptococcus mutans.MicrobiologyOpen · 2020Article
- Metabolic control of virulence factor production in Staphylococcus aureus.Current opinion in microbiology · 2020Review
- Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027.PloS one · 2019Article
- Guanine Limitation Results in CodY-Dependent and -Independent Alteration of Staphylococcus aureus Physiology and Gene Expression.Journal of bacteriology · 2018Article
- Article
- CodY, a master integrator of metabolism and virulence in Gram-positive bacteria.Current genetics · 2017Review
- The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism.Nucleic acids research · 2016Article
- Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors.Scientific reports · 2016Article
- De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo.Journal of bacteriology · 2016Article
- Interplay of CodY and ScoC in the Regulation of Major Extracellular Protease Genes of Bacillus subtilis.Journal of bacteriology · 2016Article
- Intermediate Levels of Bacillus subtilis CodY Activity Are Required for Derepression of the Branched-Chain Amino Acid Permease, BraB.PLoS genetics · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
The global regulator CodY controls the expression of dozens of metabolic genes and genes mediating adaptation to nutrient availability in many low-G+C Gram-positive bacteria. Branched-chain amino acids L-isoleucine, L-leucine, and L-valine (ILV) activate CodY both in vivo and in vitro, and genes that direct their synthesis (ilv, ybgE, and ywaA) are highly repressed by CodY, creating a potential negative feedback loop. The nucleoside triphosphate GTP also activates CodY in vitro, but the evidence for activation by GTP in vivo is limited and indirect. We constructed a Bacillus subtilis strain (ybgE bcd ywaA) that is unable to convert branched-chain α-keto acids to ILV or to use ILV as a precursor for branched-chain fatty acid synthesis. Unexpectedly, the strain was not viable on rich medium. Supplementing rich medium with short, branched-chain fatty acids or derepressing expression of genes for de novo ILV synthesis bypassed the original lethality, restoring growth and showing that the lack of viability was due to insufficient intracellular production of the precursors of branched-chain fatty acids. Spontaneous extragenic suppressor mutants that arose in the triple mutant population proved to have additional mutations in guaA or guaB or codY. Expression of ILV biosynthetic genes in codY mutants was increased. The gua mutations caused guanine/guanosine auxotrophy and led to partial derepression of direct CodY-repressed targets, including ILV biosynthetic genes, under conditions similar to those that caused the original lethality. We conclude that a guanine derivative, most likely GTP, controls CodY activity in vivo.
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