ArticleACS chemical biology2014
High-throughput screening using the differential radial capillary action of ligand assay identifies ebselen as an inhibitor of diguanylate cyclases.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 120 citations in OpenAlex.
- Updates on therapeutic targeting of diguanylate cyclase for addressing bacterial infections: A comprehensive review.World journal of microbiology & biotechnology · 2025Review
- Targeted nanomedicines for the treatment ofMaterials today. Bio · 2025Review
- Echinacoside reduces intracellular c-di-GMP levels and potentiates tobramycin activity against Pseudomonas aeruginosa biofilm aggregates.NPJ biofilms and microbiomes · 2025Article
- Harnessing Cyclic di-GMP Signaling: A Strategic Approach to Combat Bacterial Biofilm-Associated Chronic Infections.Current microbiology · 2025Review
- Impact and applications of cyclic di-GMP second messenger signaling in biotechnology and medicine.Sustainable microbiology · 2025Review
- Beyond Antibiotics: What the Future Holds.Antibiotics (Basel, Switzerland) · 2024Review
- Intestinal biofilms: pathophysiological relevance, host defense, and therapeutic opportunities.Clinical microbiology reviews · 2024Review
- FhlA is a Formate Binding Protein.bioRxiv : the preprint server for biology · 2024Article
- Ebselen: A Promising Repurposing Drug to Treat Infections Caused by Multidrug-Resistant Microorganisms.Interdisciplinary perspectives on infectious diseases · 2024Review
- Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023Review
- Molecular responses during bacterial filamentation reveal inhibition methods of drug-resistant bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance.Frontiers in cellular and infection microbiology · 2023Review
- Ebselen Optimized the Therapeutic Effects of Silver Nanoparticles for Periodontal Treatment.International journal of nanomedicine · 2023Article
- The Association between Biofilm Formation and Antimicrobial Resistance with Possible Ingenious Bio-Remedial Approaches.Antibiotics (Basel, Switzerland) · 2022Review
- Transcriptional Profiling of Pseudomonas aeruginosa Infections.Advances in experimental medicine and biology · 2022Review
- Controlling Biofilm Development Through Cyclic di-GMP Signaling.Advances in experimental medicine and biology · 2022Review
- Strategies and Approaches for Discovery of Small Molecule Disruptors of Biofilm Physiology.Molecules (Basel, Switzerland) · 2021Review
- Identification of small molecules that interfere with c-di-GMP signaling and induce dispersal of Pseudomonas aeruginosa biofilms.NPJ biofilms and microbiomes · 2021Article
- Review
- Alternative Approaches for the Management of Diabetic Foot Ulcers.Frontiers in microbiology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The rise of bacterial resistance to traditional antibiotics has motivated recent efforts to identify new drug candidates that target virulence factors or their regulatory pathways. One such antivirulence target is the cyclic-di-GMP (cdiGMP) signaling pathway, which regulates biofilm formation, motility, and pathogenesis. Pseudomonas aeruginosa is an important opportunistic pathogen that utilizes cdiGMP-regulated polysaccharides, including alginate and pellicle polysaccharide (PEL), to mediate virulence and antibiotic resistance. CdiGMP activates PEL and alginate biosynthesis by binding to specific receptors including PelD and Alg44. Mutations that abrogate cdiGMP binding to these receptors prevent polysaccharide production. Identification of small molecules that can inhibit cdiGMP binding to the allosteric sites on these proteins could mimic binding defective mutants and potentially reduce biofilm formation or alginate secretion. Here, we report the development of a rapid and quantitative high-throughput screen for inhibitors of protein-cdiGMP interactions based on the differential radial capillary action of ligand assay (DRaCALA). Using this approach, we identified ebselen as an inhibitor of cdiGMP binding to receptors containing an RxxD domain including PelD and diguanylate cyclases (DGC). Ebselen reduces diguanylate cyclase activity by covalently modifying cysteine residues. Ebselen oxide, the selenone analogue of ebselen, also inhibits cdiGMP binding through the same covalent mechanism. Ebselen and ebselen oxide inhibit cdiGMP regulation of biofilm formation and flagella-mediated motility in P. aeruginosa through inhibition of diguanylate cyclases. The identification of ebselen provides a proof-of-principle that a DRaCALA high-throughput screening approach can be used to identify bioactive agents that reverse regulation of cdiGMP signaling by targeting cdiGMP-binding domains.
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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.