Voriconazole inhibits cross-kingdom interactions between Candida albicans and Actinomyces viscosus through the ergosterol pathway

Abstract Candida albicans and Actinomyces viscosus are prominent microbes associated with root caries. This study was to investigate the effect of C. albicans on A. viscosus biofilms and to identify the mechanisms associated with this interaction. A. viscosus, C. albicans strains (wide type and mutants) were involved to form biofilms in vitro and in vivo , which were subsequently analyzed via crystal violet assays and scanning electron microscopy to investigate the effect of C. albicans on A. viscosus growth. A viable plate count and survival curve from C. albicans mutants and A. viscosus combinations were used to identify which pathway of C. albicans was crucial for cross-kingdom interactions. Voriconazole was employed to block their interactions both in vitro and in vivo . The scanning electron microscopy, fluorescence in situ hybridization, quantitative polymerase chain reaction and survival curve analyses were performed to evaluate the activities of voriconazole on C. albicans and A. viscosus interactions. The biomass and virulence of mixed-species biofilms were significantly enhanced compared to the A. viscosus biofilm alone. However, these were not observed in the mixed-species biofilms with the C. albicans mutant erg11Δ/Δ in vitro and in vivo , indicating that the azoles may work on the mixed-species biofilms. As expect, voriconazole can effectively reduce the biomass of mixed-species biofilms. High concentration of voriconazole (1 μg/ml) reduced the abundance of C. albicans , while low concentration of voriconazole (0.25 μg/ml) blocked their interactions same as the effect of erg11Δ/Δ mutant. Voriconazole may be a candidate strategy to combat root caries pathogens.