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

Abstract

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.

Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms

“…Systemic infections with C. albicans are mostly induced using the mouse tail vein infection model system, where between 10 4 and 10 6 Candida cells are injected in the lateral tail vein 288 289 . Whereas for normal virulence assays the inbred lines BALB/c or C57bl/6 are mainly used, for antifungal drug screening, outbred lines such as ICR or CD-1 should be used 183 290 .…”

In Vitro Anticandidal Activity and Mechanism of a Polyoxovanadate Functionalized by Zn-Fluconazole Complexes

“…[ 19 , 20 ]. Based on our previous studies, the fungal membrane is the target of polyoxotungstates [ 21 ], and the antibacterial polyoxotungstates uptake in the cell were preferentially located on the membrane with intact composition [ 22 , 23 ]. Some examples have been reported that the pumps, channels, metalbotropic receptors, lipid structures are all the potential biological targets for decavanadate [ 14 ].…”

Dimethyl disulfide exerts antifungal activity against Sclerotinia minor by damaging its membrane and induces systemic resistance in host plants

“…ultrastructural studies were performed. Because cell wall and cell membrane are the primary targets of several fungicides 33 , we examined the integrity of cell wall and cell membrane by measuring the electrolyte leakage in DMDS-treated or untreated hyphae after incubation for 4 days. Almost 49.2% of electrolyte leakage was observed in the treatment condition as compared to 8.2% in the control ( Supplementary Fig.…”