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Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.
Singh, B N; Upreti, D K; Singh, B R; Pandey, G; Verma, S; Roy, S; Naqvi, A H; Rawat, A K S.
Afiliación
  • Singh BN; Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India rawataks@rediffmail.com dk.upreti@nbri.res.in bn.singh@nbri.res.in.
  • Upreti DK; Lichenology Laboratory, Plant Biodiversity and Conservation Biology Division, CSIR-National Botanical Research Institute, Lucknow, India rawataks@rediffmail.com dk.upreti@nbri.res.in bn.singh@nbri.res.in.
  • Singh BR; Centre of Excellence in Materials Science (Nanomaterials), Department of Applied Physics, Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
  • Pandey G; Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India.
  • Verma S; Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India.
  • Roy S; Department of BioMedical Engineering, Faculty of Electronics and Communication, Brno University of Technology, Brno, Czech Republic.
  • Naqvi AH; Centre of Excellence in Materials Science (Nanomaterials), Department of Applied Physics, Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
  • Rawat AK; Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India rawataks@rediffmail.com dk.upreti@nbri.res.in bn.singh@nbri.res.in.
Antimicrob Agents Chemother ; 59(4): 2153-68, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25645848
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quercetina / Candida albicans / Fluconazol / Apoptosis / Farmacorresistencia Fúngica / Percepción de Quorum / Antifúngicos / Antioxidantes Idioma: En Revista: Antimicrob Agents Chemother Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quercetina / Candida albicans / Fluconazol / Apoptosis / Farmacorresistencia Fúngica / Percepción de Quorum / Antifúngicos / Antioxidantes Idioma: En Revista: Antimicrob Agents Chemother Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos