ArticleProceedings of the National Academy of Sciences of the United States of America2014
Metabolic sensor governing bacterial virulence in Staphylococcus aureus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 103 citations in OpenAlex.
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- The osteoclast intracellular environment fosters bacterial growth duringbioRxiv : the preprint server for biology · 2026Article
- CcpA promotesmLife · 2025Article
- First-in-class inhibitors of SbnA reduce siderophore production in Staphylococcus aureus.The FEBS journal · 2025Article
- Linking Virulence and Iron Limitation Response inJournal of proteome research · 2025Article
- Design, synthesis and optimization of TarO inhibitors as multifunctional antibiotics against Methicillin-resistant Staphylococcus aureus.npj antimicrobials and resistance · 2025Article
- Characterization and immunoprotective efficacy of a fumarate reductaseFrontiers in microbiology · 2025Article
- Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.Nature microbiology · 2024Article
- Staphylococcal aconitase expression during iron deficiency is controlled by an sRNA-driven feedforward loop and moonlighting activity.Nucleic acids research · 2024Article
- Citrate serves as a signal molecule to modulate carbon metabolism and iron homeostasis in Staphylococcus aureus.PLoS pathogens · 2024Article
- Exploring the targetome of IsrR, an iron-regulated sRNA controlling the synthesis of iron-containing proteins inFrontiers in microbiology · 2024Article
- IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function.Frontiers in immunology · 2024Article
- Article
- Impact of the pentose phosphate pathway on metabolism and pathogenesis of Staphylococcus aureus.PLoS pathogens · 2023Article
- Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO.Nature communications · 2023Article
- Article
- First Record of the Rare SpeciesPathogens (Basel, Switzerland) · 2022Article
- Regulation of Staphylococcal Capsule by SarZ is SigA-Dependent.Journal of bacteriology · 2022Article
- RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression.Nature communications · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An effective metabolism is essential to all living organisms, including the important human pathogen Staphylococcus aureus. To establish successful infection, S. aureus must scavenge nutrients and coordinate its metabolism for proliferation. Meanwhile, it also must produce an array of virulence factors to interfere with host defenses. However, the ways in which S. aureus ties its metabolic state to its virulence regulation remain largely unknown. Here we show that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, binds to and activates the catabolite control protein E (CcpE) of S. aureus. Using structural and site-directed mutagenesis studies, we demonstrate that two arginine residues (Arg145 and Arg256) within the putative inducer-binding cavity of CcpE are important for its allosteric activation by citrate. Microarray analysis reveals that CcpE tunes the expression of 126 genes that comprise about 4.7% of the S. aureus genome. Intriguingly, although CcpE is a major positive regulator of the TCA-cycle activity, its regulon consists predominantly of genes involved in the pathogenesis of S. aureus. Moreover, inactivation of CcpE results in increased staphyloxanthin production, improved ability to acquire iron, increased resistance to whole-blood-mediated killing, and enhanced bacterial virulence in a mouse model of systemic infection. This study reveals CcpE as an important metabolic sensor that allows S. aureus to sense and adjust its metabolic state and subsequently to coordinate the expression of virulence factors and bacterial virulence.
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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.