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

The antifungal activities of heteropolytungstates, α-1,2,3-K 6 H[SiW 9 V 3 O 40 ] (SiW-3), K 13 [Ce(SiW 11 O 39 ) 2 ]·17H 2 O (SiW-5), K 13 [Eu(SiW 11 O 39 ) 2 ]·25H 2 O (SiW-10), K 6 PV 3 W 9 O 40 (PW-6), α-K 4 PVW 11 O 40 (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 μ M 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 (LD 50 ) 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.