{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:55:00Z","timestamp":1789084500032,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Quorum sensing (QS) regulates group behaviors of\n Candida albicans<\/jats:named-content>\n such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by\n C. albicans<\/jats:named-content>\n , is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of\n C. albicans<\/jats:named-content>\n infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (\n Usnea<\/jats:named-content>\n longissima<\/jats:named-content>\n ), can be implemented as a sensitizing agent for FCZ-resistant\n C. albicans<\/jats:named-content>\n NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons\u2014biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of\n C. albicans<\/jats:named-content>\n infections.\n <\/jats:p>","DOI":"10.1128\/aac.03599-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T01:04:54Z","timestamp":1422925494000},"page":"2153-2168","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing"],"prefix":"10.1128","volume":"59","author":[{"given":"B. N.","family":"Singh","sequence":"first","affiliation":[{"name":"Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. K.","family":"Upreti","sequence":"additional","affiliation":[{"name":"Lichenology Laboratory, Plant Biodiversity and Conservation Biology Division, CSIR-National Botanical Research Institute, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. R.","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Materials Science (Nanomaterials), Department of Applied Physics, Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Verma","sequence":"additional","affiliation":[{"name":"Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of BioMedical Engineering, Faculty of Electronics and Communication, Brno University of Technology, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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