ArticleProceedings of the National Academy of Sciences of the United States of America2015
Key driving forces in the biosynthesis of autoinducing peptides required for staphylococcal virulence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Natural products shape microbial ecology and disease in the cystic fibrosis airway.Natural product reports · 2026Review
- Quorum-quenching enzymes as next-generation antibiofilm therapeutics: mechanisms, applications, and future perspectives.World journal of microbiology & biotechnology · 2026Review
- Experimental, Genomic, and Structural Evidence Supporting Putative PET-Hydrolases in Thermophilic Bacteria Isolated From Hot Springs in Cajamarca, Peru.MicrobiologyOpen · 2026Article
- RiPP recognition elements evolved to prevent pathway interference through leader peptide discrimination.Nature communications · 2026Article
- EngineeredBiochemistry · 2026Article
- A Small Molecule That Inhibits the Quorum Sensing Receptor AgrC inJournal of the American Chemical Society · 2026Article
- Phytochemical Quorum-Sensing Inhibitors Against Bacterial Pathogens: Mechanisms of Action and Translational Challenges.Current issues in molecular biology · 2026Review
- Hijacking the signal: a critical evaluation of quorum sensing inhibitors as a next-generation approach against Staphylococcus aureus.Cell communication and signaling : CCS · 2026Review
- Harnessing chemical communication in plant-microbiome and intra-microbiome interactions.Journal of Zhejiang University. Science. B · 2025Review
- Molecular mimicry: ecology, evolution, and applications of doppelgänger peptides.Trends in biochemical sciences · 2025Review
- Molecular Mechanisms of Virulence Regulation inAccounts of chemical research · 2025Article
- Targeting quorum sensing for manipulation of commensal microbiota.BMC biotechnology · 2024Review
- Determinants of maturation of theJournal of bacteriology · 2024Article
- Proteases Involved in Leader Peptide Removal during RiPP Biosynthesis.ACS bio & med chem Au · 2024Review
- Virulence attributes of successful methicillin-resistantClinical microbiology reviews · 2023Review
- Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation inBiochemistry · 2023Article
- Quorum-sensing, intra- and inter-species competition in the staphylococci.Microbiology (Reading, England) · 2023Review
- Chemical and biomolecular insights into theIsrael journal of chemistry · 2023Article
- Conformational analysis and interaction of theFrontiers in chemistry · 2023Article
- Characterization of MroQ-Dependent Maturation and Export of the Staphylococcus aureus Accessory Gene Regulatory System Autoinducing Peptide.Infection and immunity · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Staphylococci produce autoinducing peptides (AIPs) as quorum-sensing signals that regulate virulence. These AIPs feature a thiolactone macrocycle that connects the peptide C terminus to the side chain of an internal cysteine. AIPs are processed from ribosomally synthesized precursors [accessory gene regulator D (AgrD)] through two proteolytic events. Formation of the thiolactone is coupled to the first of these and involves the activity of the integral membrane protease AgrB. This step is expected to be thermodynamically unfavorable, and therefore, it is unclear how AIP-producing bacteria produce sufficient amounts of the thiolactone-containing intermediate to drive quorum sensing. Herein, we present the in vitro reconstitution of the AgrB-dependent proteolysis of an AgrD precursor from Staphylococcus aureus. Our data show that efficient thiolactone production is driven by two unanticipated features of the system: (i) membrane association of the thiolactone-containing intermediate, which stabilizes the macrocycle, and (ii) rapid degradation of the C-terminal proteolysis fragment AgrD(C), which affects the reaction equilibrium position. Cell-based studies confirm the intimate link between AIP production and intracellular AgrD(C) levels. Thus, our studies explain the chemical principles that drive AIP production, including uncovering a hitherto unknown link between quorum sensing and peptide turnover.
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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.