{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T15:44:58Z","timestamp":1780674298950,"version":"3.54.1"},"reference-count":121,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents, encompassing a wide variety of different chemical structures and mechanisms of action, were tested during our experiments. The antibacterial activity of the compounds was tested using the broth microdilution method. Screening and semi-quantitative assessment of QS-inhibition by the compounds was performed using QS-signal molecule-producing and indicator strains. Results: Fourteen pharmaceutical agents showed antibacterial activity in the tested concentration range, while eight drugs (namely 5-fluorouracil, metamizole-sodium, cisplatin, methotrexate, bleomycin, promethazine, chlorpromazine, and thioridazine) showed dose-dependent QS-inhibitory activity in the in vitro model systems applied during the experiments. Conclusions: Virulence inhibitors represent an attractive alternative strategy to combat bacterial pathogens more efficiently. Some of the tested compounds could be considered potential QS-inhibitory agents, warranting further experiments involving additional model systems to establish the extent of their efficacy.<\/jats:p>","DOI":"10.3390\/antibiotics8040270","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-0365","authenticated-orcid":false,"given":"M\u00e1ri\u00f3","family":"Gajd\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, D\u00f3m t\u00e9r 10, 6720 Szeged, Hungary"},{"name":"Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4499-388X","authenticated-orcid":false,"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3201\/eid2305.161556","article-title":"The Discovery of Penicillin\u2014New Insights after More Than 75 Years of Clinical Use","volume":"23","author":"Gaynes","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20140082","DOI":"10.1098\/rstb.2014.0082","article-title":"Tackling the threat of antimicrobial resistance: From policy to sustainable action","volume":"370","author":"Shallcross","year":"2015","journal-title":"Philos Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2147\/IDR.S173867","article-title":"Antibiotic resistance: A rundown of a global crisis","volume":"11","author":"Aslam","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMp1408040","article-title":"Antibiotic Resistance\u2014Problems, Progress, and Prospects","volume":"371","author":"Nathan","year":"2014","journal-title":"NEJM"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis","volume":"19","author":"Cassini","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","first-page":"31","article-title":"Extra deaths due to pandrug resistant bacteria: A survey of the literature","volume":"60","year":"2019","journal-title":"Eg\u00e9szs\u00e9gfejleszt\u00e9s"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1086\/533452","article-title":"Federal funding for the study of antimicrobial resistance in nosocomial pathogens: No ESKAPE","volume":"197","author":"Rice","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/595011","article-title":"Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America","volume":"48","author":"Boucher","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2475067","DOI":"10.1155\/2016\/2475067","article-title":"Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens","volume":"2016","author":"Santajit","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1039\/C9NJ00563C","article-title":"Pronounced activity of aromatic selenocyanates against multidrug resistant ESKAPE bacteria","volume":"43","author":"Nasim","year":"2019","journal-title":"New J. Chem."},{"key":"ref_11","unstructured":"World Health Organization (2019, October 27). Antimicrobial Resistance: Global Report on Surveillance. Available online: http:\/\/apps.who.int\/iris\/bitstream\/10665\/112642\/1\/9789241564748_eng.pdf?ua=1."},{"key":"ref_12","unstructured":"(2019, October 27). CDC Antibiotic\/Antimicrobial Resistance (AR\/AMR), Available online: https:\/\/www.cdc.gov\/drugresistance\/biggest_threats.html."},{"key":"ref_13","unstructured":"(2019, October 27). The Bacterial Challenge: Time to React. ECDC\/EMEA Joint Technical Report (2009). Available online: http:\/\/ecdc.europa.eu\/en\/publications\/Publications\/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","article-title":"Antibiotic resistance-the need for global solutions","volume":"13","author":"Laxminarayan","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","unstructured":"O\u2019Neill, J. (2019, October 27). Antimicrobial resistance: Tackling a crisis for the health and wealth of nations. Available online: https: \/\/amr-review.org\/sites\/default\/files\/AMRReviewPaper-Tacklingacrisisforthehealthandwealthofnations_1.pdf."},{"key":"ref_16","unstructured":"Gajd\u00e1cs, M., and Szab\u00f3, A. (2019). Physicians\u2019 opinions towards antibiotic use and resistance in the southeastern region of Hungary. Orv. Hetil., accepted."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cmi.2017.08.026","article-title":"What is antimicrobial stewardship?","volume":"23","author":"Dyar","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3389\/fmicb.2014.00217","article-title":"Antibiotic alternatives: The substitution of antibiotics in animal husbandry?","volume":"5","author":"Cheng","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.mib.2003.08.003","article-title":"Why is big Pharma getting out of antibacterial drug discovery?","volume":"6","author":"Projan","year":"2003","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1465-0691.2004.1008.x","article-title":"Antibacterial drug discovery: Is small pharma the solution?","volume":"10","author":"Boggs","year":"2004","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3109\/03009734.2014.896437","article-title":"Discovery and preclinical development of new antibiotics","volume":"119","author":"Hughes","year":"2014","journal-title":"Ups. J. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M. (2019). The Concept of an Ideal Antibiotic: Implications for Drug Design. Molecules, 24.","DOI":"10.3390\/molecules24050892"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms for antibiotic discovery","volume":"12","author":"Lewis","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., and Albericio, F. (2019). Antibiotic Resistance: From the Bench to Patients. Antibiotics, 8.","DOI":"10.3390\/antibiotics8030129"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.tim.2016.06.009","article-title":"Antibiotic Adjuvants: Rescuing Antibiotics from Resistance","volume":"24","author":"Wright","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s10529-017-2311-8","article-title":"New approaches to antibiotic discovery","volume":"39","author":"Kealey","year":"2017","journal-title":"Biotechnol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/IDR.S159957","article-title":"Bezlotoxumab for the prevention of Clostridium difficile infection: A review of current evidence and safety profile","volume":"12","author":"Alonso","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1128\/CMR.00037-09","article-title":"Three Decades of \u03b2-Lactamase Inhibitors","volume":"23","author":"Drawz","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2174\/138161211795703726","article-title":"Microbial Efflux Pump Inhibition: Tactics and Strategies","volume":"17","author":"Tegos","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Spengler, G., Kincses, A., Gajdacs, M., and Amaral, L. (2017). New Roads Leading to Old Destinations: Efflux Pumps as Targets to Reverse Multidrug Resistance in Bacteria. Molecules, 22.","DOI":"10.3390\/molecules22030468"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.3762\/bjoc.14.239","article-title":"Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections","volume":"14","author":"Calvert","year":"2018","journal-title":"Beilstein. J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nrmicro1818","article-title":"The biology and future prospects of antivirulence therapies","volume":"6","author":"Cegelski","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","first-page":"1795","article-title":"The arsenal of pathogens and antivirulence therapeutic strategies for disarming them","volume":"10","author":"Brannon","year":"2016","journal-title":"Drug Des. Devel."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrd.2017.23","article-title":"Different drugs for bad bugs: Antivirulence strategies in the age of antibiotic resistance","volume":"16","author":"Dickey","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1039\/C9MD00146H","article-title":"On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome","volume":"10","author":"Lyons","year":"2019","journal-title":"Med. Chem. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4155\/fmc-2016-0227","article-title":"Disarming pathogens: Benefits and challenges of antimicrobials that target bacterial virulence instead of growth and viability","volume":"9","author":"Totsika","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1007\/s00253-015-6436-1","article-title":"Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens","volume":"99","author":"Reen","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"344.e1","DOI":"10.1016\/j.cmi.2014.11.016","article-title":"Collateral damage from oral ciprofloxacin versus nitrofurantoin in outpatients with urinary tract infections: A culture-free analysis of gut microbiota","volume":"21","author":"Stewardson","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.7150\/ijbs.24612","article-title":"Review of Drug Repositioning Approaches and Resources","volume":"14","author":"Xue","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.micro.55.1.165","article-title":"Quorum Sensing in Bacteria","volume":"55","author":"Miller","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jiang, Q., Chen, J., Yang, C., Yin, Y., and Yao, K. (2019, October 27). Quorum Sensing: A Prospective Therapeutic Target for Bacterial Diseases. Available online: https:\/\/www.hindawi.com\/journals\/bmri\/2019\/2015978\/.","DOI":"10.1155\/2019\/2015978"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature24624","article-title":"Bacterial quorum sensing: The progress and promise of an emerging research area","volume":"551","author":"Whiteley","year":"2017","journal-title":"Nature"},{"key":"ref_43","first-page":"e02331","article-title":"Bacterial Quorum Sensing and Microbial Community Interactions","volume":"9","author":"Abisado","year":"2018","journal-title":"mBio"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1128\/jb.95.3.975-979.1968","article-title":"Aspects of light production by Photobacterium fischeri","volume":"95","author":"Kempner","year":"1968","journal-title":"J. Bacteriol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1128\/jb.104.1.313-322.1970","article-title":"Cellular control of the synthesis and activity of the bacterial luminescent system","volume":"104","author":"Nealson","year":"1970","journal-title":"J. Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1128\/jb.109.3.1101-1105.1972","article-title":"Inhibition and activation of bacterial luciferase synthesis","volume":"109","author":"Eberhard","year":"1972","journal-title":"J. Bacteriol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/femsre\/fuv038","article-title":"Quorum quenching: Role in nature and applied developments","volume":"40","author":"Dessaux","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., and Urb\u00e1n, E. (2019). Epidemiological Trends and Resistance Associated with Stenotrophomonas maltophilia Bacteremia: A 10-Year Retrospective Cohort Study in a Tertiary-Care Hospital in Hungary. Diseases, 7.","DOI":"10.3390\/diseases7020041"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0065-2164(07)62007-3","article-title":"Quorum Sensing: Fact, Fiction, and Everything in Between","volume":"62","author":"Turovskiy","year":"2007","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"a012427","DOI":"10.1101\/cshperspect.a012427","article-title":"Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control","volume":"2","author":"Rutherford","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fcimb.2019.00074","article-title":"Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition","volume":"9","author":"Cardoso","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2174\/1574891X11308010012","article-title":"Bacterial quorum sensing inhibitors: Attractive alternatives for control of infectious pathogens showing multiple drug resistance","volume":"8","author":"Bhardwaj","year":"2013","journal-title":"Recent Pat. Anti-Infect. Drug Discov."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd3078","article-title":"How to improve R&D productivity: The pharmaceutical industry\u2019s grand challenge","volume":"9","author":"Paul","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fmicb.2019.00041","article-title":"Drug Repurposing for the Treatment of Bacterial and Fungal Infections","volume":"10","author":"Smani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Gatta, V., Ilina, P., Porter, A., McElroy, S., and Tammela, P. (2019). Targeting Quorum Sensing: High-Throughput Screening to Identify Novel LsrK Inhibitors. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123112"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1128\/AAC.01283-08","article-title":"Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing Inhibitors","volume":"53","author":"Yang","year":"2009","journal-title":"AAC"},{"key":"ref_58","unstructured":"Soo, V.W.C., Kwan, B.W., Quezada, H., Castillo-Ju\u00e1rez, I., P\u00e9rez-Eretza, B., Garc\u00eda-Contreras, S.J., Mart\u00ednez-V\u00e1zquez, M., Wood, T.K., and Garc\u00eda-Contreras, R. (2019, October 27). Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections. Available online: http:\/\/www.eurekaselect.com\/145957\/article."},{"key":"ref_59","first-page":"5983","article-title":"Possible Biological and Clinical Applications of Phenothiazines","volume":"37","author":"Varga","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3389\/fphar.2013.00168","article-title":"Efflux pumps of Gram-negative bacteria: What they do, how they do it, with what and how to deal with them","volume":"4","author":"Amaral","year":"2014","journal-title":"Front. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1021\/cr030117g","article-title":"Antitumor antibiotics: Bleomycin, enediynes, and mitomycin","volume":"105","author":"Galm","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/ajcp\/52.2.130","article-title":"Actinomycin and Antitumor Antibiotics","volume":"52","author":"Young","year":"1969","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Spengler, G., Gajd\u00e1cs, M., Mar\u0107, M.A., Dom\u00ednguez-\u00c1lvarez, E., and Sanmart\u00edn, C. (2019). Organoselenium Compounds as Novel Adjuvants of Chemotherapy Drugs-A Promising Approach to Fight Cancer Drug Resistance. Molecules, 24.","DOI":"10.3390\/molecules24020336"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e3952","DOI":"10.7717\/peerj.3952","article-title":"Statins: Antimicrobial resistance breakers or makers?","volume":"5","author":"Ko","year":"2017","journal-title":"PeerJ"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/infdis\/jit550","article-title":"Statin Therapy Reduces the Mycobacterium tuberculosis Burden in Human Macrophages and in Mice by Enhancing Autophagy and Phagosome Maturation","volume":"209","author":"Parihar","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_67","first-page":"e01296","article-title":"Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa","volume":"62","author":"Baldelli","year":"2018","journal-title":"AAC"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13756-018-0314-4","article-title":"In vitro activity of ivermectin against Staphylococcus aureus clinical isolates","volume":"7","author":"Ashraf","year":"2018","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"750","DOI":"10.3389\/fmicb.2015.00750","article-title":"Repurposing celecoxib as a topical antimicrobial agent","volume":"6","author":"Thangamani","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/ptr.6042","article-title":"Bioactive compounds from the African medicinal plant Cleistochlamys kirkii as resistance modifiers in bacteria","volume":"32","author":"Kincses","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/ptr.3010","article-title":"Inhibition of quorum-sensing signals by essential oils","volume":"24","author":"Varga","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fmicb.2014.00178","article-title":"Antivirulence activity of azithromycin in Pseudomonas aeruginosa","volume":"5","author":"Imperi","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1093\/jac\/dks002","article-title":"Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model","volume":"67","author":"Christensen","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"ftz011","DOI":"10.1093\/femspd\/ftz011","article-title":"Aeruginosa flow-cell biofilms are enhanced by repeated phage treatments but can be eradicated by phage\u2013ciprofloxacin combination\u2014Monitoring the phage\u2013P. aeruginosa biofilms interactions","volume":"77","author":"Henriksen","year":"2019","journal-title":"Pathog. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.3389\/fmicb.2018.03286","article-title":"Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia","volume":"9","author":"Richter","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nprot.2009.205","article-title":"In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect","volume":"5","author":"Bjarnsholt","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1080\/23744235.2019.1640389","article-title":"Resistance trends and epidemiology of Aeromonas and Plesiomonas infections (RETEPAPI): A 10-year retrospective survey","volume":"51","year":"2019","journal-title":"Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/0147-619X(78)90042-2","article-title":"Fingerprints of Agrobacterium Ti plasmids","volume":"1","author":"Sciaky","year":"1978","journal-title":"Plasmid"},{"key":"ref_79","doi-asserted-by":"crossref","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":"ref_80","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1574-6976.2007.00071.x","article-title":"Quorum sensing in Serratia","volume":"31","author":"Givskov","year":"2007","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1073\/pnas.96.4.1639","article-title":"Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A new family of genes responsible for autoinducer production","volume":"96","author":"Surette","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","first-page":"396","article-title":"The significance of bacterial quorum sensing (QS) inhibition in antivirulence therapy","volume":"Volume XI","year":"2019","journal-title":"Diszcipl\u00edn\u00e1k Tal\u00e1lkoz\u00e1sa\u2013Nyelvek \u00e9s Kult\u00far\u00e1k \u00c9rintkez\u00e9se"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., Buri\u00e1n, K., and Terhes, G. (2019). Resistance Levels and Epidemiology of Non-Fermenting Gram-Negative Bacteria in Urinary Tract Infections of Inpatients and Outpatients (RENFUTI): A 10-Year Epidemiological Snapshot. Antibiotics, 8.","DOI":"10.3390\/antibiotics8030143"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1365-2672.2009.04205.x","article-title":"The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents","volume":"107","author":"Othman","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2217\/fmb.12.84","article-title":"Beyond nutrition: Health-promoting foods by quorum-sensing inhibition","volume":"7","author":"Givskov","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_86","first-page":"1","article-title":"Curcumin liposomes interfere with quorum sensing system of Aeromonas sobria and in silico analysis","volume":"7","author":"Ding","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep22571","article-title":"Antibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogens","volume":"6","author":"Thangamani","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1128\/AEM.05992-11","article-title":"Food as a source for quorum sensing inhibitors: Iberin from horseradish revealed as a quorum sensing inhibitor of Pseudomonas aeruginosa","volume":"78","author":"Jakobsen","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7325","DOI":"10.1007\/s00253-013-4875-0","article-title":"The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability","volume":"97","author":"Antoniani","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1074\/jbc.M116.770552","article-title":"Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors","volume":"292","author":"Paczkowski","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"16529","DOI":"10.1073\/pnas.1904700116","article-title":"A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s00248-017-0949-3","article-title":"Reducing Virulence and Biofilm of Pseudomonas aeruginosa by Potential Quorum Sensing Inhibitor Carotenoid: Zeaxanthin","volume":"74","author":"Aksoydan","year":"2017","journal-title":"Microb. Ecol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1128\/IAI.00630-07","article-title":"Differential Effects of Epinephrine, Norepinephrine, and Indole on Escherichia coli O157:H7 Chemotaxis, Colonization, and Gene Expression","volume":"75","author":"Bansal","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jff.2015.05.016","article-title":"Cranberry (Vaccinium macrocarpon) oligosaccharides decrease biofilm formation by uropathogenic Escherichia coli","volume":"17","author":"Sun","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_95","first-page":"1","article-title":"Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by downregulating saeRS","volume":"7","author":"Duan","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.3389\/fmicb.2018.01952","article-title":"Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas aeruginosa by Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.micpath.2018.03.012","article-title":"Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid","volume":"118","author":"Rajkumari","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1128\/AAC.05919-11","article-title":"Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing","volume":"56","author":"Jakobsen","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1590\/S1517-83822013000300029","article-title":"Cancer drugs inhibit morphogenesis in the human fungal pathogen, Candida albicans","volume":"44","author":"Routh","year":"2013","journal-title":"Braz. J. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Poli, J.-P., Guinoiseau, E., de Rocca Serra, D., Sutour, S., Paoli, M., Tomi, F., Quilichini, Y., Berti, L., and Lorenzi, V. (2018). Anti-Quorum Sensing Activity of 12 Essential Oils on chromobacterium violaceum and Specific Action of cis-cis-p-Menthenolide from Corsican Mentha suaveolens ssp. Insularis. Molecules, 23.","DOI":"10.3390\/molecules23092125"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.1128\/AAC.00834-16","article-title":"Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis","volume":"60","author":"Hendrix","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.1128\/AAC.03137-14","article-title":"In Vitro Analysis of Finasteride Activity against Candida albicans Urinary Biofilm Formation and Filamentation","volume":"58","author":"Lown","year":"2014","journal-title":"AAC"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-20617-5","article-title":"The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus","volume":"8","author":"Yeo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.4314\/ahs.v16i4.29","article-title":"Glyceryl trinitrate is a novel inhibitor of quorum sensing in Pseudomonas aeruginosa","volume":"16","author":"Abbas","year":"2016","journal-title":"Afr. Health Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1128\/AAC.02810-15","article-title":"Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs","volume":"60","author":"Ogundeji","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/2000-1967-211","article-title":"In vitro investigation of the antibacterial effect of ketamine","volume":"113","author":"Gocmen","year":"2008","journal-title":"Ups. J. Med. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1089\/sur.2007.036","article-title":"Local Anesthetics as Antimicrobial Agents: A Review","volume":"9","author":"Johnson","year":"2008","journal-title":"Surg. Infect."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"808","DOI":"10.4314\/ahs.v17i3.24","article-title":"Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa","volume":"17","author":"Abbas","year":"2017","journal-title":"Afr. Health Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.chembiol.2017.05.027","article-title":"Attenuating Staphylococcus aureus Virulence by Targeting Flotillin Protein Scaffold Activity","volume":"24","author":"Koch","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1128\/AAC.01952-12","article-title":"New Life for an Old Drug: The Anthelmintic Drug Niclosamide Inhibits Pseudomonas aeruginosa Quorum Sensing","volume":"57","author":"Imperi","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.lfs.2018.03.013","article-title":"Exploring the impact of parthenolide as anti-quorum sensing and anti-biofilm agent against Pseudomonas aeruginosa","volume":"199","author":"Kalia","year":"2018","journal-title":"Life Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e01846","DOI":"10.1128\/AAC.01846-16","article-title":"Repurposing Toremifene for Treatment of Oral Bacterial Infections","volume":"61","author":"Gerits","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_113","first-page":"315","article-title":"Action of cholecalciferol and alpha-tocopherol on Staphylococcus aureus efflux pumps","volume":"15","author":"Tintino","year":"2016","journal-title":"EXCLI J."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Kwieci\u0144ska-Pir\u00f3g, J., Skowron, K., Bogiel, T., Bia\u0142ucha, A., Przekwas, J., and Gospodarek-Komkowska, E. (2019). Vitamin C in the Presence of Sub-Inhibitory Concentration of Aminoglycosides and Fluoroquinolones Alters Proteus mirabilis Biofilm Inhibitory Rate. Antibiotics, 8.","DOI":"10.3390\/antibiotics8030116"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1024\/0300-9831\/a000268","article-title":"Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs","volume":"88","author":"Andrade","year":"2018","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.sjbs.2015.09.004","article-title":"Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism","volume":"24","author":"Andrade","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.biopha.2014.10.011","article-title":"Enhancement of the antibiotic activity of aminoglycosides by alpha-tocopherol and other cholesterol derivates","volume":"68","author":"Andrade","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1007\/s10620-018-5122-4","article-title":"Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors","volume":"63","author":"Hojo","year":"2018","journal-title":"Dig. Dis Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1094\/MPMI.1998.11.11.1119","article-title":"Production of acyl-homoserine lactone quorum-sensing signals by gram-negative plant-associated bacteria","volume":"11","author":"Cha","year":"1998","journal-title":"Mol. Plant. Microbe Interact."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1128\/AEM.00593-07","article-title":"Inhibition of Quorum Sensing in Serratia marcescens AS-1 by Synthetic Analogs of N-Acylhomoserine Lactone","volume":"73","author":"Morohoshi","year":"2007","journal-title":"Appl. Env. Microbiol."},{"key":"ref_121","first-page":"151","article-title":"Culture media supplemented with inorganic salts improve the growth and viability of several bacterial strains","volume":"60","author":"Kerekes","year":"2016","journal-title":"Acta Biol. Szeged."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:43:10Z","timestamp":1760190190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":121,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["antibiotics8040270"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics8040270","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]}}}