Abstract
The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents.
Highlights
Despite recent progress in the clinical management, invasive fungal infections are still a tricky problem and have a high mortality
When minimal inhibitory concentration (MIC)-like assays were performed for FLC in the presence of fixed subinhibitory concentrations of Gla (4 mg/ml), the median MICs of FLC decreased from 128 mg/ml to 1 mg/ml in resistant strains (32-fold to 512-fold reductions)
According to the analysis of fractional inhibitory concentration index (FICI) method, synergism was observed in all 25 tested strains (FICIs,0.2)
Summary
Despite recent progress in the clinical management, invasive fungal infections are still a tricky problem and have a high mortality. Synergistic antifungal effect of Gla and FLC against FLC-resistant clinical isolates of C. albicans and other yeast fungi (i.e. C_neoformans, C. tropicalis, C. parapsilosis, C. krusei and C. glabratas) and the possible mechanisms were investigated. We tested antifungal effects of Gla alone or in combination with FLC in FLC-sensitive C. albicans and the other yeast strains (C. neoformans, C. tropicalis, C. krusei, C. parapsilosis and C. glabratas) (Table 2).
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