Interactions between Human Phagocytes and Candida albicans Biofilms Alone and in Combination with Antifungal Agents

Background. Biofilm formation is an important component of vascular catheter infections caused by Candida albicans. Little is known about the interactions between human phagocytes, antifungal agents, and Candida biofilms. Methods. The interactions between C. albicans biofilms and human phagocytes alone and in combination with anidulafungin or voriconazole were investigated and compared with their corresponding planktonic counterparts by means of an in vitro biofilm model with clinical intravascular and green fluorescent protein (GFP)-expressing strains. Phagocyte-mediated 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 were visualized by confocal microscopy. Oxidative burst was evaluated by flow cytometric measurement of dihydrorhodamine 123 oxidation, and cytokine release was measured by enzyme-linked immunosorbent assay. Results. Phagocytes alone and in combination with antifungal agents induced less damage against biofilms compared with planktonic cells. However, additive effects occurred between phagocytes and anidulafungin against Candida biofilms. Confocal microscopy demonstrated the absence of phagocytosis within biofilms but marked destruction caused by anidulafungin and phagocytes. Anidulafungin but not voriconazole elicited tumor necrosis factor a release from phagocytes compared with that from untreated biofilms. Conclusions. C. albicans within biofilms are more resistant to phagocytic host defenses but are susceptible to additive effects between phagocytes and an echinocandin.