ArticleACS chemical biology2018
Structure-Function Analyses of the N-Butanoyl l-Homoserine Lactone Quorum-Sensing Signal Define Features Critical to Activity in RhlR.
Article in ACS chemical biology, 2018. 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.
- Chemical Probes that Target a Dissociative LuxR-Type Quorum Sensing Receptor in Gram-Negative Bacteria.ACS chemical biology · 2025Article
- Sulfonyl Homoserine Lactones Are Tunable Probes to Inhibit the Quorum Sensing Receptor RhlR and Reduce Swarming Motility inACS infectious diseases · 2025Article
- Effects on LuxR-Regulated Bioluminescence of Cyclodextrin-Acyl-L-Homoserine Lactone Hybrids.Chembiochem : a European journal of chemical biology · 2025Article
- Interaction of plant-derived metabolites and rhizobiome functions enhances drought stress tolerance.Genome biology · 2025Article
- Insights into the Mechanisms of Small Molecule-Induced Agonism and Antagonism of a Quorum Sensing Receptor inJournal of the American Chemical Society · 2025Article
- Article
- Silyl-Lipid FunctionalizedACS chemical biology · 2025Article
- Lipid-Modulated, Graduated Inhibition of N-Glycosylation Pathway Priming Suggests Wide Tolerance of ER Proteostasis to Stress.ACS central science · 2025Article
- Developing Gingerol-Based Analogs againstACS omega · 2024Article
- Interspecies Crosstalk via LuxI/LuxR-Type Quorum Sensing Pathways Contributes to Decreased Nematode Survival in Coinfections ofACS chemical biology · 2024Article
- Characterization of natural product inhibitors of quorum sensing reveals competitive inhibition ofMicrobiology spectrum · 2024Article
- A Systematic Hierarchical Virtual Screening Model for RhlR Inhibitors Based on PCA, Pharmacophore, Docking, and Molecular Dynamics.International journal of molecular sciences · 2024Article
- Abiotic Small Molecule Inhibitors and Activators of the LasR Quorum Sensing Receptor inACS infectious diseases · 2024Article
- Characterization of natural product inhibitors of quorum sensing inbioRxiv : the preprint server for biology · 2024Article
- Unveiling the hidden language of bacteria: anti-quorum sensing strategies for gram-negative bacteria infection control.Archives of microbiology · 2024Review
- How Nanoparticles Help in Combating Chronic Wound Biofilms Infection?International journal of nanomedicine · 2024Review
- Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation inMicrobiology (Reading, England) · 2023Article
- Targeting Multidrug-Recalcitrant Pseudomonas aeruginosa Biofilms: Combined-Enzyme Treatment Enhances Antibiotic Efficacy.Antimicrobial agents and chemotherapy · 2023Article
- Autoinducer-fluorophore conjugates enable FRET in LuxR proteins in vitro and in cells.Nature chemical biology · 2022Article
- The Molecular Architecture ofMarine drugs · 2022Review
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Authors and funding
10 authors.
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Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that coordinates the production of many virulence phenotypes at high population density via quorum sensing (QS). The LuxR-type receptor RhlR plays an important role in the P. aeruginosa QS process, and there is considerable interest in the development of chemical approaches to modulate the activity of this protein. RhlR is activated by a simple, low molecular weight N-acyl l-homoserine lactone signal, N-butanoyll-homoserine lactone (BHL). Despite the emerging prominence of RhlR in QS pathways, there has been limited exploration of the chemical features of the BHL scaffold that are critical to its function. In the current study, we sought to systematically delineate the structure-activity relationships (SARs) driving BHL activity for the first time. A focused library of BHL analogues was designed, synthesized, and evaluated in cell-based reporter gene assays for RhlR agonism and antagonism. These investigations allowed us to define a series of SARs for BHL-type ligands and identify structural motifs critical for both activation and inhibition of the RhlR receptor. Notably, we identified agonists that have ∼10-fold higher potencies in RhlR relative to BHL, are highly selective for RhlR agonism over LasR, and are active in the P. aeruginosa background. These compounds and the SARs reported herein should pave a route toward new chemical strategies to study RhlR in P. aeruginosa.
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