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In vitro and in vivo antifungal activities and mechanism of heteropolytungstates against Candida species


The antifungal activities of heteropolytungstates, α-1,2,3-K6H[SiW9V3O40] (SiW-3), K13[Ce(SiW11O39)2]·17H2O (SiW-5), K13[Eu(SiW11O39)2]·25H2O (SiW-10), K6PV3W9O40 (PW-6), α-K4PVW11O40 (PW-8), were screened in 29 Candida albicans, 8 Candida glabrata, 3 Candida krusei, 2 Candida parapsilosis, 1 Candida tropicalis, and 1 Cryptococcus neoformans strains using the CLSI M27-A3 method. SiW-5 had the highest efficacy with a minimum inhibitory concentration (MIC) values of <0.2-10.2 μM in vitro. The antifungal mechanism, acute toxicity and in vivo antifungal activity of SiW-5 were then evaluated in C. albicans. The results showed that SiW-5 damaged the fungal cell membrane, reduce the ergosterol content and its main mode of action was through inhibition of ergosterol biosynthesis. Real-time PCR showed that ERG1, ERG7, ERG11 and ERG28 were all significantly upregulated by SiW-5. An acute toxicity study showed the 50% lethal dose (LD50) of SiW-5 for ICR mice was 1651.5 mg/kg. And in vivo antifungal studies demonstrated that SiW-5 reduced both the morbidity and fungal burden of mice infected with C. albicans. This study demonstrates that SiW-5 is a potential antifungal candidate against the Candida species.

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