{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:50:18Z","timestamp":1788954618274,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> is a Gram-negative opportunistic pathogen that poses a significant threat to public health due to its inherent and acquired resistance to multiple antibiotics. This mini-review explores the antimicrobial potential of 5-fluorouracil (5-FU), a chemotherapeutic agent normally used in oncology, and currently under investigation for its bacteriostatic and antibiofilm effects against <jats:italic>P. aeruginosa<\/jats:italic>. 5-FU functions by inhibiting thymidylate synthase, disrupting nucleotide metabolism, and interfering with essential bacterial processes, such as quorum sensing. Studies <jats:italic>in vitro<\/jats:italic> have demonstrated its ability to inhibit biofilm creation and decrease virulence, but findings about its impact on preformed biofilms have been contradictory. Synergistic interactions between 5-FU and antibiotics, especially gentamicin, have shown promise in enhancing antibacterial effectiveness. The aim of this mini-review was to consolidate current findings, pinpoint research gaps, and suggest future directions for potentially repurposing 5-FU as an adjunctive treatment for <jats:italic>P. aeruginosa<\/jats:italic>. By placing the current evidence in context, we hope to guide further studies toward determining the clinical viability of 5-FU as a treatment option against this formidable pathogen.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1584479","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:26:43Z","timestamp":1752816403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of 5-fluorouracil on Pseudomonas aeruginosa: impact on virulence, biofilm formation, and bacterial growth"],"prefix":"10.3389","volume":"16","author":[{"given":"Amani A.","family":"Niazy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May M.","family":"Alrashed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurahman A.","family":"Niazy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00253-009-1860-8","article-title":"5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound","volume":"82","author":"Attila","year":"2009","journal-title":"Appl. Microbiol. Biotechnol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s44259-024-00047-2","article-title":"Drug combinations targeting antibiotic resistance","volume":"2","author":"Bogn\u00e1r","year":"2024","journal-title":"npj Antimicrob. Resis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e49123","DOI":"10.1371\/journal.pone.0049123","article-title":"The lon protease is essential for full virulence in Pseudomonas aeruginosa","volume":"7","author":"Breidenstein","year":"2012","journal-title":"PLoS ONE"},{"key":"B4","unstructured":"Pseudomonas aeruginosa infection\n          \n          2021"},{"key":"B5","unstructured":"CDC partners estimate healthcare cost of antibiotic-resistant Infections"},{"key":"B6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3109\/09546634.2010.507704","article-title":"Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders","volume":"23","author":"Ceilley","year":"2012","journal-title":"J. Dermatol. Treat."},{"key":"B7","doi-asserted-by":"publisher","first-page":"654","DOI":"10.3390\/molecules21050654","article-title":"Flavin-dependent thymidylate synthase as a new antibiotic target","volume":"21","author":"Choi","year":"2016","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1128\/CMR.00022-14","article-title":"Pharmacokinetics and pharmacodynamics of aerosolized antibacterial agents in chronically infected cystic fibrosis patients","volume":"27","author":"Dalhoff","year":"2014","journal-title":"Clin. Microbiol. Rev"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.3390\/ijms23095029","article-title":"Giving drugs a second chance: antibacterial and antibiofilm effects of ciclopirox and ribavirin against cystic fibrosis Pseudomonas aeruginosa strains","volume":"23","author":"Di Bonaventura","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0035223","DOI":"10.1128\/spectrum.00352-23","article-title":"Repurposing high-throughput screening identifies unconventional drugs with antibacterial and antibiofilm activities against Pseudomonas aeruginosa under experimental conditions relevant to cystic fibrosis","volume":"11","author":"Di Bonaventura","year":"2023","journal-title":"Microbiol. Spectr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1099\/mic.0.000860","article-title":"Microbe profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat","volume":"166","author":"Diggle","year":"2020","journal-title":"Microbiology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1345\/aph.1E099","article-title":"Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa","volume":"39","author":"Drobnic","year":"2005","journal-title":"Ann. Pharmacother"},{"key":"B13","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.addr.2017.09.015","article-title":"Nanoparticle-based local antimicrobial drug delivery","volume":"127","author":"Gao","year":"2018","journal-title":"Adv. Drug Deliv. Rev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/2049-632X.12039","article-title":"Resistance to the quorum-quenching compounds brominated furanone C-30 and 5-fluorouracil in Pseudomonas aeruginosa clinical isolates","volume":"68","author":"Garc\u00eda-Contreras","year":"2013","journal-title":"Pathog. Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s002800000189","article-title":"Pharmacokinetics and pharmacodynamic effects of 5-fluorouracil given as a one-hour intravenous infusion","volume":"47","author":"Grem","year":"2001","journal-title":"Cancer Chemother. Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/179663a0","article-title":"Fluorinated pyrimidines, a new class of tumor inhibitory compounds","volume":"179","author":"Heidelberger","year":"1957","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1002\/jps.20607","article-title":"Pharmacokinetics of 5-fluorouracil in the hamster following inhalation delivery of lipid-coated nanoparticles","volume":"95","author":"Hitzman","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0196506","DOI":"10.1371\/journal.pone.0196506","article-title":"Bacterial versus human thymidylate synthase: kinetics and functionality","volume":"13","author":"Islam","year":"2018","journal-title":"PLoS ONE"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.3390\/ijms22063128","article-title":"Molecular sciences Pseudomonas aeruginosa: an audacious pathogen with an adaptable arsenal of virulence factors","volume":"22","author":"Jurado-Mart\u00edn","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"737","DOI":"10.5301\/ijao.5000027","article-title":"Antibiotic-induced biofilm formation","volume":"34","author":"Kaplan","year":"2011","journal-title":"Int. J. Artif. Organs"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e00217","DOI":"10.1128\/mSphere.00217-16","article-title":"A high-content, phenotypic screen identifies fluorouridine as an inhibitor of pyoverdine biosynthesis and Pseudomonas aeruginosa virulence","volume":"1","author":"Kirienko","year":"2016","journal-title":"MSphere"},{"key":"B22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s13238-014-0100-x","article-title":"The hierarchy quorum sensing network in Pseudomonas aeruginosa","volume":"6","author":"Lee","year":"2015","journal-title":"Protein Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/S0149-2918(01)80078-3","article-title":"A pharmacokinetic evaluation of 0.5% and 5% fluorouracil topical cream in patients with actinic keratosis","volume":"23","author":"Levy","year":"2001","journal-title":"Clin. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The challenge of efflux-mediated antibiotic resistance in gram-negative bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin. Microbiol. Rev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1128\/CMR.00040-09","article-title":"Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms","volume":"22","author":"Lister","year":"2009","journal-title":"Clin. Microbiol. Rev"},{"key":"B26","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-Fluorouracil: mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"15779","DOI":"10.3390\/ijms232415779","article-title":"Role of efflux pumps on antimicrobial resistance in Pseudomonas aeruginosa","volume":"23","author":"Lorusso","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq516","article-title":"Antibiotic dosing in critical illness","author":"McKenzie","year":"2011","journal-title":"J. Antimicrob. Chemother"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1285386","DOI":"10.3389\/fbiom.2023.1285386","article-title":"Mini-review antimicrobial smart materials: the future's defense against wound infections","volume":"2","author":"Monroe","year":"2023","journal-title":"Front. Biomater. Sci"},{"key":"B30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fcimb.2017.00039","article-title":"Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence","volume":"7","author":"Moradali","year":"2017","journal-title":"Front. Cell. Infect. Microbiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4550","DOI":"10.1128\/AEM.00169-07","article-title":"Transcriptome analysis reveals that multidrug efflux genes are upregulated to protect Pseudomonas aeruginosa from pentachlorophenol stress","volume":"73","author":"Muller","year":"2007","journal-title":"Appl. Environ. Microbiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.3390\/microorganisms12112257","article-title":"5-fluorouracil inhibits bacterial growth and reduces biofilm in addition to having synergetic effects with gentamicin against Pseudomonas aeruginosa","volume":"12","author":"Niazy","year":"2024","journal-title":"Microorganisms"},{"key":"B33","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1248\/cpb.c20-00086","article-title":"Present situation and future progress of inhaled lung cancer therapy: necessity of inhaled formulations with drug delivery functions","volume":"68","author":"Okuda","year":"2020","journal-title":"Chem Pharm Bull"},{"key":"B34","doi-asserted-by":"publisher","first-page":"37853","DOI":"10.1038\/srep37853","article-title":"Optimising antibiotic usage to treat bacterial infections","volume":"6","author":"Paterson","year":"2016","journal-title":"Sci. Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e2300103","DOI":"10.1002\/ardp.202300103","article-title":"Synthesis and antimicrobial testing of 5-fluorouracil derivatives","volume":"356","author":"Patil","year":"2023","journal-title":"Archiv. Der. Pharmazie"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.3390\/microorganisms11051210","article-title":"Relative abundance and detection of pseudomonas aeruginosa from chronic wound infections globally","volume":"11","author":"Phan","year":"2023","journal-title":"Microorganisms"},{"key":"B37","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1080\/14787210.2020.1752665","article-title":"Repurposed anti-cancer drugs: the future for anti-infective therapy?","volume":"18","author":"Quezada","year":"2020","journal-title":"Expert Rev. Anti. Infect. Ther"},{"key":"B38","doi-asserted-by":"publisher","first-page":"251","DOI":"10.2217\/pgs.10.167","article-title":"5-Fluorouracil pharmacogenomics: still rocking after all these years?","volume":"12","author":"Scartozzi","year":"2011","journal-title":"Pharmacogenomics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1093\/nar\/gkab251","article-title":"5-Fluorouracil blocks quorum-sensing of biofilm-embedded methicillin-resistant Staphylococcus aureus in mice","volume":"49","author":"Sedlmayer","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/jjco\/hyn127","article-title":"Development history and concept of an oral anticancer agent S-1 (TS-1\u00ae): its clinical usefulness and future vistas","volume":"39","author":"Shirasaka","year":"2009","journal-title":"Jpn. J. Clin. Oncol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"121","DOI":"10.4155\/tde.14.94","article-title":"Tobramycin inhalation powder: an efficient and efficacious therapy for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis","volume":"6","author":"Somayaji","year":"2015","journal-title":"Ther. Deliv"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.2174\/1568026616666160930131737","article-title":"Repurposing of anticancer drugs for the treatment of bacterial infections","volume":"17","author":"Soo","year":"2016","journal-title":"Curr. Top. Med. Chem"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13756-020-00859-7","article-title":"Comparative evaluation of the effect of different growth media on in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients","volume":"9","author":"S\u00f6rensen","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0135571","DOI":"10.1371\/journal.pone.0135571","article-title":"Assessments of thioridazine as a helper compound to dicloxacillin against methicillin-resistant Staphylococcus aureus: in vivo trials in a mouse peritonitis model","volume":"10","author":"Stenger","year":"2015","journal-title":"PLoS ONE"},{"key":"B45","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination therapy for treatment of infections with gram-negative bacteria","volume":"25","author":"Tamma","year":"2012","journal-title":"Clin. Microbiol. Rev"},{"key":"B46","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jbiotec.2014.09.003","article-title":"Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies","volume":"191","author":"Taylor","year":"2014","journal-title":"J. Biotechnol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/j.1751-7915.2008.00060.x","article-title":"Uracil influences quorum sensing and biofilm formation in Pseudomonas aeruginosa and fluorouracil is an antagonist","volume":"2","author":"Ueda","year":"2009","journal-title":"Microb. Biotechnol"},{"key":"B48","volume-title":"WHO Publishes List of Bacteria for which New Antibiotics are Urgently Needed","year":"2017"},{"key":"B49","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/nrclinonc.2014.51","article-title":"Standing the test of time: targeting thymidylate biosynthesis in cancer therapy","volume":"11","author":"Wilson","year":"2014","journal-title":"Nat. Rev. Clin. Oncol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1592\/phco.22.12.972.33596","article-title":"Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients","volume":"22","author":"Wood","year":"2002","journal-title":"Pharmacotherapy"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/B978-0-12-397169-2.00087-1","article-title":"\u201cChapter 87 - Klebsiella Pneumoniae and Pseudomonas Aeruginosa,\u201d","author":"Wu","year":"2015","journal-title":"Molecular Medical Microbiology (Second Edition)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"15493","DOI":"10.3390\/ijms242015493","article-title":"The combination of antibiotic and non-antibiotic compounds improves antibiotic efficacy against multidrug-resistant bacteria","volume":"24","author":"Xiao","year":"2023","journal-title":"Int. J. Mol. Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e01603","DOI":"10.1128\/AAC.01603-17","article-title":"Interplay between antibiotic efficacy and drug-induced lysis underlies enhanced biofilm formation at subinhibitory drug concentrations","volume":"62","author":"Yu","year":"2018","journal-title":"Antimicrob. Agents Chemother"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1584479\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:26:45Z","timestamp":1752816405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1584479\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":53,"alternative-id":["10.3389\/fmicb.2025.1584479"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1584479","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"article-number":"1584479"}}