ArticlePLoS genetics2018
Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
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- Genotype-Environment-Driven Dysbiosis in the Skin Microbiome of Ichthyosis.The Journal of investigative dermatology · 2026Article
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- Metabolic and regulatory adaptations of Staphylococcus epidermidis to host stresses.FEMS microbiology reviews · 2026Review
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- Effects of Nutritional Conditions on Growth, Biofilm Formation, and Enterotoxin Production inInternational journal of molecular sciences · 2025Article
- Inactivation of branched-chain amino acid uptake halts Staphylococcus aureus growth and induces bacterial quiescence within macrophages.PLoS pathogens · 2025Article
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- Universal receptive system as a novel regulator of transcriptomic activity of Staphylococcus aureus.Microbial cell factories · 2025Article
- Regulatory dynamics of arginine metabolism in Staphylococcus aureus.Biochemical Society transactions · 2024Review
- CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis inJournal of bacteriology · 2024Article
- Functional and Proteomic Dissection of the Contributions of CodY, SigB and the Hibernation Promoting Factor HPF to Interactions ofJournal of proteome research · 2024Article
- ThemBio · 2024Article
- In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.Molecular microbiology · 2024Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
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Abstract
Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.
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