ArticleChembiochem : a European journal of chemical biology2015
Increasing AIP Macrocycle Size Reveals Key Features of agr Activation in Staphylococcus aureus.
Article in Chembiochem : a European journal of chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- EngineeredBiochemistry · 2026Article
- Molecular Mechanisms of Virulence Regulation inAccounts of chemical research · 2025Article
- 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
- Tannin extracted fromFrontiers in microbiology · 2023Article
- Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides.Chemical reviews · 2022Review
- Inner residues of macrothiolactone in autoinducer peptides I/IV circumvent spontaneousRSC chemical biology · 2022Article
- Discovery of quorum quenchers targeting the membrane-embedded sensor domain of theChemical communications (Cambridge, England) · 2020Article
- Targeted and untargeted analysis of secondary metabolites to monitor growth and quorum sensing inhibition for methicillin-resistant Staphylococcus aureus (MRSA).Journal of microbiological methods · 2020Article
- Conformational Switch to a β-Turn in a Staphylococcal Quorum Sensing Signal Peptide Causes a Dramatic Increase in Potency.Journal of the American Chemical Society · 2020Article
- Hybrid Antimicrobial Peptide TargetingFrontiers in microbiology · 2020Article
- Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation.Nature chemistry · 2019Article
- Identification of a Molecular Latch that Regulates Staphylococcal Virulence.Cell chemical biology · 2019Article
- Simplified Autoinducing Peptide Mimetics with Single-Nanomolar Activity Against the Staphylococcus aureus AgrC Quorum Sensing Receptor.ACS infectious diseases · 2019Article
- Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms.Current topics in medicinal chemistry · 2018Review
- Therapeutic Targeting of theFrontiers in microbiology · 2018Review
- Simplified AIP-II Peptidomimetics Are Potent Inhibitors of Staphylococcus aureus AgrC Quorum Sensing Receptors.Chembiochem : a European journal of chemical biology · 2017Article
- Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence.Cell chemical biology · 2017Article
- Structure-Function Analyses of a Staphylococcus epidermidis Autoinducing Peptide Reveals Motifs Critical for AgrC-type Receptor Modulation.ACS chemical biology · 2016Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The agr locus in the commensal human pathogen, Staphylococcus aureus, is a two-promoter regulon with allelic variability that produces a quorum-sensing circuit involved in regulating virulence within the bacterium. Secretion of unique autoinducing peptides (AIPs) and detection of their concentrations by AgrC, a transmembrane receptor histidine kinase, coordinates local bacterial population density with global changes in gene expression. The finding that staphylococcal virulence can be inhibited through antagonism of this quorum-sensing pathway has fueled tremendous interest in understanding the structure-activity relationships underlying the AIP-AgrC interaction. The defining structural feature of the AIP is a 16-membered, thiolactone-containing macrocycle. Surprisingly, the importance of ring size on agr activation or inhibition has not been explored. In this study, we address this deficiency through the synthesis and functional analysis of AIP analogues featuring enlarged and reduced macrocycles. Notably, this study is the first to interrogate AIP function by using both established cell-based reporter gene assays and newly developed in vitro AgrC-I binding and autophosphorylation activity assays. Based on our data, we present a model for robust agr activation involving a cooperative, three-points-of-contact interaction between the AIP macrocycle and AgrC.
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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.