{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T05:51:03Z","timestamp":1791697863234,"version":"4.3.4"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Development of drug resistance in opportunistic pathogens is one of the major healthcare challenges associated with infection management. Combination therapy has many advantages due to the simultaneous action of two drugs on two separate cellular targets. However, selection of the drugs should offer safety and synergistic interaction against most of the strains. Here, the efficacy of antibiotics in combination with quercetin, a natural flavonoid capable of targeting quorum sensing was tested against biofilm-forming\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    strains previously isolated from catheter associated urinary tract infection. Based on the antibiotic susceptibility pattern, synergistic effect of quercetin with selected antibiotics (levofloxacin, ceftriaxone, gentamycin, tobramycin and amikacin) was tested at the fractional concentrations of MIC by the checkerboard method and the fractional inhibitory concentration index (FIC\n                    <jats:sub>i<\/jats:sub>\n                    ) was calculated to estimate the synergistic effect. Effect of the synergistic combinations were further tested using time-kill assay, and against biofilm formation and biofilm cell viability. Cytotoxicity assays were performed using Human Embryonic Kidney 293T cells (HEK-293T) using the effective drug combinations with respective controls. The biofilm formation and biofilm cell viability were drastically affected with quercetin and selected antibiotics combinations with \u226580% inhibition.\n                    <jats:italic>In vitro<\/jats:italic>\n                    infection studies showed that all the strains could exert significant cell killing (68 to 85%) and the drug combinations decreased the infection rate significantly by reducing the cell killing effect of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    (p&lt;0.05). The synergistic effect of quercetin is attributed to its quorum sensing inhibitory properties. These findings indicate that quercetin along with existing antibiotics can potentiate the treatment against\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    infection and may reduce the selection pressure due to antibiotic overuse.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0241304","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T13:34:02Z","timestamp":1604669642000},"page":"e0241304","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":112,"title":["RETRACTED: Potential synergistic activity of quercetin with antibiotics against multidrug-resistant clinical strains of Pseudomonas aeruginosa"],"prefix":"10.1371","volume":"15","author":[{"given":"Chembili","family":"Vipin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1508-5305","authenticated-orcid":true,"given":"Kanekar","family":"Saptami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathima","family":"Fida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musliyarakath","family":"Mujeeburahiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha S.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Athmika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-9266","authenticated-orcid":true,"given":"Ananthapadmanabha Bhagwath","family":"Arun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9187-6395","authenticated-orcid":true,"given":"Punchappady Devasya","family":"Rekha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"pone.0241304.ref001","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/apm.13010","article-title":"The environmental occurrence of Pseudomonas aeruginosa","author":"S Crone","year":"2020","journal-title":"APMIS"},{"key":"pone.0241304.ref002","article-title":"Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy","author":"SA Kraemer","year":"2019","journal-title":"Microorganisms"},{"key":"pone.0241304.ref003","article-title":"Antibiotic resistance profiles of Pseudomonas aeruginosa isolated from various Greek aquatic environments","author":"P Olga","year":"2016","journal-title":"FEMS Microbiol Ecol"},{"key":"pone.0241304.ref004","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.tim.2016.01.008","article-title":"Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections","author":"C Winstanley","year":"2016","journal-title":"Trends Microbiol"},{"key":"pone.0241304.ref005","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s10096-015-2323-z","article-title":"Biofilm-specific antibiotic tolerance and resistance","author":"I. Olsen","year":"2015","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pone.0241304.ref006","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1021\/acs.jproteome.6b00058","article-title":"Pseudomonas aeruginosa Cell Membrane Protein Expression from Phenotypically Diverse Cystic Fibrosis Isolates Demonstrates Host-Specific Adaptations","author":"KS Kamath","year":"2016","journal-title":"J Proteome Res"},{"key":"pone.0241304.ref007","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gendis.2019.04.001","article-title":"Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review","author":"P Pachori","year":"2019","journal-title":"Genes Dis"},{"issue":"5","key":"pone.0241304.ref008","first-page":"310","article-title":"Current concepts in combination antibiotic therapy for critically ill patients","author":"A Ahmed","year":"2014","journal-title":"Crit Care Med: peer-reviewed, official publication of Indian Society of Critical Care Medicine"},{"key":"pone.0241304.ref009","doi-asserted-by":"crossref","first-page":"20321","DOI":"10.1038\/srep20321","article-title":"The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release","author":"G Brackman","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0241304.ref010","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","author":"JE Paczkowski","year":"2017","journal-title":"J Biol Chem"},{"key":"pone.0241304.ref011","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jmii.2014.03.012","article-title":"Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1","author":"HS Vasavi","year":"2016","journal-title":"J Microbiol Immunol Infect"},{"key":"pone.0241304.ref012","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40360-016-0083-8","article-title":"The synergy and mode of action of quercetin plus amoxicillin against amoxicillin-resistant Staphylococcus epidermidis","author":"S Siriwong","year":"2016","journal-title":"BMC Pharmacol Toxicol"},{"key":"pone.0241304.ref013","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12906-015-0580-0","article-title":"Antibiotic additive and synergistic action of rutin, morin and quercetin against methicillin resistant Staphylococcus aureus","author":"MU Amin","year":"2015","journal-title":"BMC Complement Altern Med"},{"key":"pone.0241304.ref014","doi-asserted-by":"crossref","first-page":"e0134684","DOI":"10.1371\/journal.pone.0134684","article-title":"Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence","author":"V Gopu","year":"2015","journal-title":"PLOS 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Strober","year":"2015","journal-title":"Curr Protoc Immunol"},{"key":"pone.0241304.ref024","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.apjtm.2017.07.021","article-title":"Medicinal plant products targeting quorum sensing for combating bacterial infections","author":"A Bouyahya","year":"2017","journal-title":"Asian Pac J Trop Med"},{"key":"pone.0241304.ref025","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3390\/md15030053","article-title":"Quorum Sensing Inhibitors from the Sea Discovered Using Bacterial N-acyl-homoserine Lactone-Based Biosensors","author":"K Saurav","year":"2017","journal-title":"Mar Drugs"},{"key":"pone.0241304.ref026","first-page":"1","article-title":"Quorum Sensing in Pseudomonas aeruginosa and Its Relationship to Biofilm Development. Introduction to Biofilm Engineering","author":"J Lin","year":"2019","journal-title":"American Chemical Society"},{"key":"pone.0241304.ref027","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.chom.2019.06.002","article-title":"Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms","author":"J Yan","year":"2019","journal-title":"Cell Host Microbe"},{"key":"pone.0241304.ref028","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s11999-016-4700-z","article-title":"Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time","author":"P Castaneda","year":"2016","journal-title":"Clin Orthop"},{"key":"pone.0241304.ref029","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/cid\/civ353","article-title":"Biofilms: An Underappreciated Mechanism of Treatment Failure and Recurrence in Vaginal Infections","author":"CA Muzny","year":"2015","journal-title":"Clin Infect Dis"},{"key":"pone.0241304.ref030","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.micpath.2017.05.014","article-title":"Phenotypic and genotypic study of biofilm formation in Enterococci isolated from urinary tract infections","author":"F Fallah","year":"2017","journal-title":"Microb Pathog"},{"key":"pone.0241304.ref031","article-title":"Tolerance and Resistance of Pseudomonas aeruginosa Biofilms to Antimicrobial Agents\u2014How P. aeruginosa Can Escape Antibiotics","author":"O Ciofu","year":"2019","journal-title":"Front Microbiol"},{"key":"pone.0241304.ref032","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.apt.2018.03.025","article-title":"ROS mediated destruction of cell membrane, growth and biofilms of human bacterial pathogens by stable metallic AgNPs functionalized from bell pepper extract and quercetin","author":"B Ahmed","year":"2018","journal-title":"Adv Powder Technol"},{"key":"pone.0241304.ref033","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/08927014.2013.788692","article-title":"Anti-biofilm activities of quercetin and tannic acid against Staphylococcus aureus","author":"J-H Lee","year":"2013","journal-title":"Biofouling"},{"key":"pone.0241304.ref034","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/jam.13073","article-title":"Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa","author":"J Ouyang","year":"2016","journal-title":"J Appl Microbiol"},{"key":"pone.0241304.ref035","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.etap.2016.11.004","article-title":"Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity","author":"PS Bustos","year":"2016","journal-title":"Environ Toxicol Pharmacol"},{"key":"pone.0241304.ref036","first-page":"160","article-title":"A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C","author":"NT Lu","year":"2016","journal-title":"Phytother Res"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0356579","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0241304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:41:46Z","timestamp":1788889306000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0241304"}},"subtitle":[],"editor":[{"given":"Yu-Wei","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,6]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0241304","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,6]]}}}