Interactions between Human Phagocytes andCandida albicansBiofilms Alone and in Combination with Antifungal Agents

Abstract

Background Biofilm formation is an important component of vascular catheter infections caused by Candida albicans. Little is known about the interactions between human phagocytes and antifungal agents on Candida biofilms. Materials and Methods The interactions of C. albicans biofilms with human phagocytes alone and in combination with anidulafungin or voriconazole were investigated and compared with their corresponding planktonic counterparts using an in vitro biofilm model with clinical intravascular and green fluorescent protein (GFP) expressing strains. Phagocyte- and antifungal agent-mediated damages were determined by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide assay and structural effects visualized by confocal microscopy. Oxidative burst was evaluated by flow cytometric measurement of dihydrorhodamine (DHR)-123 oxidation and cytokine release measured by EIA. Results Phagocytes alone or in combination with antifungal agents induced less damage against biofilms as compared to planktonic cells. However, additive effects occurred between phagocytes and anidulafungin against Candida biofilms. Confocal microscopy demonstrated absence of phagocytosis within biofilms, but marked destruction caused by anidulafungin and phagocytes. Anidulafungin but not voriconazole elicited a TNF-α release from phagocytes compared with untreated biofilms. Conclusions Candida albicans within biofilms are more resistant to phagocytic host defenses but are susceptible to additive effects between phagocytes and an echinocandin.

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