Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, 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 C. albicans 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 (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans 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-biofilm 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 C. albicans infections.

• MeSH
• antifungální látky farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• apoptóza účinky léků   MeSH
• biofilmy účinky léků   MeSH
• Candida albicans účinky léků   MeSH
• faktory virulence metabolismus   MeSH
• flukonazol farmakologie   MeSH
• fungální léková rezistence účinky léků   MeSH
• hyfy účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• quercetin farmakologie   MeSH
• quorum sensing účinky léků   MeSH
• Usnea chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hirtusneanoside, a new O-deoxyglycoside of a dimeric tetrahydroxanthone, was isolated from the lichen Usnea hirta. Its structure, including the absolute configuration, was determined by means of extensive spectroscopic data (UV, IR, MS, CD, 1D and 2D NMR) and chemical degradation. Hirtusneanoside has a unique structure comprising L-rhamnopyranoside of a tetrahydroxanthone dimer and showed growth inhibitory activities against Gram-positive bacteria.

• MeSH
• antibakteriální látky farmakologie   chemie   izolace a purifikace   MeSH
• Bacillus subtilis účinky léků   MeSH
• financování organizované MeSH
• glykosidy farmakologie   chemie   izolace a purifikace   MeSH
• molekulární struktura MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• Staphylococcus aureus účinky léků   MeSH
• Usnea chemie   MeSH
• xantony farmakologie   chemie   izolace a purifikace   MeSH
• Geografické názvy
• Česká republika MeSH