Abstract
Context: 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. Materials and 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 MICSH and/or MICfluconazole treatments, 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. Results and conclusion: 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.
Highlights
The incidence of invasive mycotic infection has increased significantly (Sardi et al 2013)
We employed 18 clinical C. albicans isolates as well as a reference strain C. albicans SC5314 to survey the antifungal effects of sodium houttuyfonate (SH) and/or fluconazole
It could be observed that the minimum inhibitory concentrations (MICs) of SH ranged from 32 to 256 lg/mL when SH was used alone, while decreased in a range of 8–64 lg/mL when used in combination with fluconazole
Summary
The incidence of invasive mycotic infection has increased significantly (Sardi et al 2013). Invasive candidiasis was reportedly able to cause as high as 40–60% mortality rates (Tobudic et al 2012). As a consequence of increased abuse of traditional antifungal agents and antibiotics, the ever-increasing rate of resistance of C. albicans, especially to fluconazole poses a serious threat to antifungal therapy, calling for urgent need in search of novel antifungal drugs. Most of the reported chemicals claimed to possess potential antimycotic functions have relatively high minimum inhibitory concentrations (MICs); these antifungals usually had strong potential of resistance reversion in fluconazole-resistant C. albicans (Quan et al 2006; Zhou et al 2012; Letscher-Bru et al 2013; Padmavathi et al 2015). Finding new drugs capable of improving the antifungal activity of fluconazole can be taken into account as an alternative way to expand the antifungal bank (Guo et al 2008)
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