Abstract

Fungal biofilms caused by Candida spp. are a major contributor to infections originating from infected biomaterial implants. Since echinocandin-class molecules interfere with the integrity of the fungal cell wall, it was hypothesized that surface-immobilized anidulafungin and micafungin could play a role in preventing fungal adhesion and biofilm formation on surfaces. Anidulafungin and micafungin were covalently coupled to biomaterial surfaces and washed. Surface-sensitive instrumental analysis quantitatively and qualitatively confirmed their presence. Analysis after washing experiments provided evidence of their covalent immobilization. The in vitro antifungal properties of surfaces were confirmed using static biofilm assays and fluorescence microscopy kinetic studies. Antifungal surface coatings eliminated 106 cfu/cm2 inoculations of Candida albicans and prevented biofilm formation and hyphal development on coated surfaces. Surfaces were successively exposed to fresh inoculum and were effective for at least five challenges in eliminating adherent yeasts. We have observed antifungal and anti-biofilm activity of surfaces bearing conjugated echinocandins, which operate through surface contact. The analytical and biological evidence suggests an antifungal mechanism for echinocandins that does not rely upon freely diffusing molecules.

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