title: Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis.
abstract: BACKGROUND
  Vulvovaginal candidiasis (VVC) is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ). Quercetin (QCT) is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm.
  
  
  METHODS
  17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm.
  
  
  RESULTS
  We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i) be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii) inhibit fungal adherence, cell surface hydrophobicity (CSH), flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii) down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv) the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ.
  
  
  CONCLUSIONS
  Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm.
authors.affiliation: Department of Gynecology, the First People's Hospital of Shangqiu, Shangqiu City, Henan Province, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: LiJuan
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005427:Flocculation; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D025301:Hyphae / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010933:Plankton / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D012333:RNA, Messenger; D015725:Fluconazole; D011794:Quercetin