ArticleJournal of the American Chemical Society2015
Small molecule disruption of quorum sensing cross-regulation in pseudomonas aeruginosa causes major and unexpected alterations to virulence phenotypes.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 164 citations in OpenAlex.
- Interaction of the polar localization protein BscR with phosphodiesterase PipA regulates virulence strategies in Pseudomonas aeruginosa.Journal of advanced research · 2026Article
- NIR-Triggered On-Demand Synergistic Therapy for Multidrug-Resistant Bacterial Infections Via a Smart Phase-Transition Hydrogel.Advanced healthcare materials · 2026Article
- Discovery of triazole-tethered glycinate and propanoate derivatives bearing a thiolactone moiety as quorum sensing inhibitors ofRSC advances · 2026Article
- Sulfonyl Homoserine Lactones Are Tunable Probes to Inhibit the Quorum Sensing Receptor RhlR and Reduce Swarming Motility inACS infectious diseases · 2025Article
- Insights into the Mechanisms of Small Molecule-Induced Agonism and Antagonism of a Quorum Sensing Receptor inJournal of the American Chemical Society · 2025Article
- Headway in Synthetic Chemistry: A Gateway for Antimicrobial Trojan Horse Strategy for Drug Repurposing Against Multi-Drug ResistantIndian journal of microbiology · 2025Review
- Silyl-Lipid FunctionalizedACS chemical biology · 2025Article
- Developing Gingerol-Based Analogs againstACS omega · 2024Article
- Transcriptome Analysis Reveals the Mechanism of Y0-C10-HSL on Biofilm Formation and Motility ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Assembly of functional microbial ecosystems: from molecular circuits to communities.FEMS microbiology reviews · 2024Review
- Design, Synthesis, and Biological Evaluation of the Quorum-Sensing Inhibitors ofMolecules (Basel, Switzerland) · 2024Article
- Unveiling the hidden language of bacteria: anti-quorum sensing strategies for gram-negative bacteria infection control.Archives of microbiology · 2024Review
- Thermo-responsive cascade antimicrobial platform for precise biofilm removal and enhanced wound healing.Burns & trauma · 2024Article
- Marine-Derived Furanones Targeting Quorum-Sensing Receptors inBioinformatics and biology insights · 2024Article
- Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections.Pharmaceutics · 2023Review
- Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation inBiochemistry · 2023Article
- Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections.Cell reports · 2023Article
- A Geneticist Transcribing the Chemical Language of Bacteria.Israel journal of chemistry · 2023Article
- Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii.Nature communications · 2023Article
- Anti-Microorganisms · 2023Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The opportunistic pathogen Pseudomonas aeruginosa uses three interwoven quorum-sensing (QS) circuits-Las, Rhl, and Pqs-to regulate the global expression of myriad virulence-associated genes. Interception of these signaling networks with small molecules represents an emerging strategy for the development of anti-infective agents against this bacterium. In the current study, we applied a chemical approach to investigate how the Las-Rhl-Pqs QS hierarchy coordinates key virulence phenotypes in wild-type P. aeruginosa. We screened a focused library of synthetic, non-native N-acyl l-homoserine lactones and identified compounds that can drastically alter production of two important virulence factors: pyocyanin and rhamnolipid. We demonstrate that these molecules act by targeting RhlR in P. aeruginosa, a QS receptor that has seen far less scrutiny to date relative to other circuitry. Unexpectedly, modulation of RhlR activity by a single compound induces inverse regulation of pyocyanin and rhamnolipid, a result that was not predicted using genetic approaches to interrogate QS in P. aeruginosa. Further, we show that certain RhlR agonists strongly repress Pqs signaling, revealing disruption of Rhl-Pqs cross-regulation as a novel mechanism for QS inhibition. These compounds significantly expand the known repertoire of chemical probes available to study RhlR in P. aeruginosa. Moreover, our results suggest that designing chemical agents to disrupt Rhl-Pqs crosstalk could be an effective antivirulence strategy to fight this common pathogen.
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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.