Synergistic Antifungal Effect of Glabridin and Fluconazole

Liu, Wei; Li, Li Ping; Zhang, Jun Dong; Li, Qun; Shen, Hui; Chen, Si Min; He, Li; Yan, Lan; Xu, Guo; An, Mao Mao; Jiang, Yuan

doi:10.1371/journal.pone.0103442

Cited by 69 publications

(46 citation statements)

References 31 publications

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“…The FIC index was determined according to reference 55 by evaluating the growth of C. albicans exposed to increasing pairwise concentrations of antimycin (0.0625 to 4 µg/ml) and candicidin (1 to 64 µg/ml). The formula used was FIC index = FIC A + FIC B, where FIC A = MIC of combination/MIC of compound A and FIC B = MIC of combination/MIC of compound B.…”

Section: Methodsmentioning

confidence: 99%

Coordinate Regulation of Antimycin and Candicidin Biosynthesis

McLean

Hoskisson

Seipke

2016

mSphere

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Natural products produced by members of the phylum Actinobacteria underpin many industrially and medically important compounds; however, the majority of the ~30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. Understanding the diversity of regulatory strategies controlling the expression of these pathways is therefore critical if their biosynthetic potential is to be explored for new drug leads. Our findings reveal that the candicidin cluster-situated regulator FscRI coordinately controls the biosynthesis of both candicidin and antimycin, which is the first observation of cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products. We anticipate that this will emerge as a major strategy by which members of the phylum Actinobacteria coordinately produce natural products, which will advance our understanding of how the expression of secondary metabolism is controlled and will aid the pursuit of “silent” biosynthetic pathway activation.

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Section: Methodsmentioning

confidence: 99%

Coordinate Regulation of Antimycin and Candicidin Biosynthesis

McLean

Hoskisson

Seipke

2016

mSphere

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“…The in vitro efficacy of various antimicrobial combinations was evaluated for all isolates according to the broth microdilution chequerboard method . The final combination concentrations of azoles and inhibitors of efflux pumps ranged from 0.008 to 16 μg/mL for VOR and from 0.5 to 512 μg/mL for FLZ and from 12.5 to 200 μg/mL for HAL, from 50 to 400 μg/mL for PTZ and CYS.…”

Section: Methodsmentioning

confidence: 99%

“…Each isolate was tested three times on different days. The data obtained by the chequerboard microdilution assays were analysed using the model‐fractional inhibitory concentration index (FICI) method based on the Loewe additivity theory . FICI was calculated by the following equation: FICI=FIC A +FIC B , where FIC A is the MIC of the combination/the MIC of drug A alone, and FIC B is the MIC of the combination/the MIC of drug B alone.…”

Section: Methodsmentioning

confidence: 99%

“…The in vitro efficacy of various antimicrobial combinations was evaluated for all isolates according to the broth microdilution chequerboard method. [30][31][32][33][34] The final combination concentrations of azoles and inhibitors of efflux pumps ranged from 0.008 to 16 μg/mL for VOR and from 0.5 to 512 μg/mL for FLZ and from 12.5 to 200 μg/mL for HAL, from 50 to 400 μg/mL for PTZ and CYS. The first drug of the combination was serially double diluted along the ordinate, while the second drug was double diluted along the abscissa of 96-well flatbottomed microtitre plates.…”

Section: Chequerboard Microdilution Assaymentioning

confidence: 99%

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The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

Iatta

Puttilli

Immediato

et al. 2016

Mycoses

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This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains.

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“…The plates were incubated at 32 C upto 48 h to observe for the zones of inhibition. Sodium benzoate (50 mg/ml and 100 mg/ml) (Lavermicocca et al, 2000;Stanojevic et al, 2009), and Fluconazone (150 mg/10 ml) (Vandeputte et al, 2012;Liu et al, 2014), known antifungal agents, were used as positive controls.…”

Section: Quantification Of Antifungal Activitymentioning

confidence: 99%