title: The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans.
abstract: BACKGROUND
  Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species.
  
  
  OBJECTIVE
  This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism.
  
  
  METHODS
  The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003.
  
  
  RESULTS
  For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed.
  
  
  CONCLUSIONS
  Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.
authors.affiliation: a Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine , Anhui University of Chinese Medicine , Hefei , China .
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: a Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine , Anhui University of Chinese Medicine , Hefei , China .
authors.forename: MengXiang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: b Laboratory of Biochemistry and Molecular Biology, School of Chinese and Western Integrative Medicine , Anhui University of Chinese Medicine , Hefei , China , and.
authors.forename: TianMing
authors.initials: T
authors.lastname: Wang
authors.affiliation: c Gynecology of Traditional Chinese Medicine, Clinical College of Traditional Chinese Medicine , Anhui University of Chinese Medicine , Hefei , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine , Anhui University of Chinese Medicine , Hefei , China .
authors.forename: ChangZhong
authors.initials: C
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D044949:Kaempferols / Q000008:administration & dosage / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D044949:Kaempferols; D026901:Membrane Transport Proteins; C006552:kaempferol; D015725:Fluconazole
keywords: Efflux pump; fluconazole resistance; gene expression; rhodamine 6G; synergism