ArticleNucleic acids research2021
5-Fluorouracil blocks quorum-sensing of biofilm-embedded methicillin-resistant Staphylococcus aureus in mice.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- The β-lactam adjuvant guanosine potentiates anti-folate antibiotics and pyrimidine synthesis inhibitors by depleting thymidine in methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- Recent Advances in Microenvironment-Responsive Materials for Periodontitis Therapy.International journal of molecular sciences · 2026Review
- The β-lactam adjuvant guanosine potentiates anti-folate antibiotics and pyrimidine synthesis inhibitors by depleting thymidine in methicillin-resistantbioRxiv : the preprint server for biology · 2026Article
- 5-Fluorouracil modulates motility and biofilm-associated gene expression in Pseudomonas aeruginosa.PloS one · 2026Article
- Quorum-Sensing Inhibitors as Potential Antibacterial Agents Against Staphylococcus aureus: A Comprehensive Review.Chemistry & biodiversity · 2026Review
- Strategies and applications of antibacterial surface-modified biomaterials.Bioactive materials · 2025Review
- Drug Repurposing: An Emerging Strategy inJournal of microbiology and biotechnology · 2025Review
- 5-Fluorouracil for the Treatment of Pustulosis Caused by Vascular Occlusion After Receiving Filler Injection.Aesthetic plastic surgery · 2025Article
- DisarmingPathogens (Basel, Switzerland) · 2025Review
- Ta-Ag Coatings on TC4: A Strategy to Leverage Bioelectric Microenvironments for Enhanced Antibacterial Activity.Biotechnology journal · 2025Article
- Drug interactions between cephalosporins and 5-FU-based chemotherapy in the treatment of patients with gastrointestinal cancer - an exploratory cohort analysis.Frontiers in pharmacology · 2025Article
- Based on quorum sensing: reverse effect of traditional Chinese medicine on bacterial drug resistance mechanism.Frontiers in cellular and infection microbiology · 2025Review
- Effect of 5-fluorouracil onFrontiers in microbiology · 2025Review
- Article
- 5-Fluorouracil Inhibits Bacterial Growth and Reduces Biofilm in Addition to Having Synergetic Effects with Gentamicin AgainstMicroorganisms · 2024Article
- Treatment of Facial Artery Embolization Caused by Polycaprolactone-based Dermal Filler with a Regimen Including 5-Fluorouracil.Plastic and reconstructive surgery. Global open · 2024Article
- Fluoropyrimidines affectBiofilm · 2024Article
- Tackling Antibiotic Resistance: Exploring 5-Fluorouracil as a Promising Antimicrobial Strategy for the Treatment ofAnimals : an open access journal from MDPI · 2024Article
- Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms.Journal of translational medicine · 2024Article
- Unveiling the Hidden Dangers: Massive Allergic Dermatitis After Hyaluronic Acid Injection.Clinical, cosmetic and investigational dermatology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Antibiotic-resistant pathogens often escape antimicrobial treatment by forming protective biofilms in response to quorum-sensing communication via diffusible autoinducers. Biofilm formation by the nosocomial pathogen methicillin-resistant Staphylococcus aureus (MRSA) is triggered by the quorum-sensor autoinducer-2 (AI-2), whose biosynthesis is mediated by methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) and S-ribosylhomocysteine lyase (LuxS). Here, we present a high-throughput screening platform for small-molecular inhibitors of either enzyme. This platform employs a cell-based assay to report non-toxic, bioavailable and cell-penetrating inhibitors of AI-2 production, utilizing engineered human cells programmed to constitutively secrete AI-2 by tapping into the endogenous methylation cycle via ectopic expression of codon-optimized MTAN and LuxS. Screening of a library of over 5000 commercial compounds yielded 66 hits, including the FDA-licensed cytostatic anti-cancer drug 5-fluorouracil (5-FU). Secondary screening and validation studies showed that 5-FU is a potent quorum-quencher, inhibiting AI-2 production and release by MRSA, Staphylococcus epidermidis, Escherichia coli and Vibrio harveyi. 5-FU efficiently reduced adherence and blocked biofilm formation of MRSA in vitro at an order-of-magnitude-lower concentration than that clinically relevant for anti-cancer therapy. Furthermore, 5-FU reestablished antibiotic susceptibility and enabled daptomycin-mediated prevention and clearance of MRSA infection in a mouse model of human implant-associated infection.
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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.