title: Synergistic in vitro activity of sodium houttuyfonate with fluconazole against clinical Candida albicans strains under planktonic growing conditions.
abstract: BACKGROUND
  Fluconazole resistance is an intractable problem of treating Candida albicans, calling for more antifungal agents to enhance the activity of fluconazole.
  
  
  OBJECTIVE
  This work investigates the anti-C. albicans activities of sodium houttuyfonate (SH) and/or fluconazole and the associated mechanism.
  
  
  METHODS
  The minimum inhibitory concentrations (MICs) of SH and fluconazole both ranging from 0.5 to 1024 μg/mL were determined by broth microdilution method in 19 C. albicans isolates, and their fractional inhibitory concentration index (FICI) was evaluated by checkerboard assay. After MICSHand/or MICfluconazoletreatments, the expressions of IFD6, PHR1, ZAP1, ADH5, BGL2, XOG1 and FKS1 were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans 1601.
  
  
  CONCLUSIONS
  The MICs of SH alone ranged from 32 to 256 μg/mL and decreased 2-16-fold in combination. SH showed strong synergism with fluconazole with FICI <0.13-0.5. In C. albicans 1601, we observed that (i) the expression of the seven genes increased notably in a range between 3.71- and 12.63-fold (p < 0.05) when SH was used alone, (ii) the combined use of SH and fluconazole slightly inhibited the expression of IFD6 and PHR1 by 1.23- and 1.35-fold (p > 0.05), but promoted evidently the expression of ZAP1, ADH5, XOG1 and FKS1 by 1.98-, 3.56-, 4.10- and 2.86-fold (p < 0.05). The results suggested SH to be a potential synergist to enhance the antifungal activity of fluconazole in C. albicans resistant isolates, and the underlying mechanism may be associated with β-1,3-glucan synthesis and transportation.
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: YanYan
authors.initials: Y
authors.lastname: Cui
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.
authors.forename: TianMing
authors.initials: T
authors.lastname: Wang
authors.affiliation: a Laboratory of Microbiology and Immunology , School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine , Hefei , China.
authors.forename: DaQiang
authors.initials: D
authors.lastname: Wu
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: D000473:Alkanes / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000494:pharmacology*; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D000473:Alkanes; D000935:Antifungal Agents; D005656:Fungal Proteins; D011509:Proteoglycans; D013447:Sulfites; D047071:beta-Glucans; C473296:sodium houttuyfonate; C010770:polysaccharide-K; D015725:Fluconazole
keywords: Synergism; ZAP1; antifungal agent; houttuynin; resistance; β-1,3-glucan