Occidiofungin inhibition of Candida biofilm formation on silicone elastomer surface

Abstract

ABSTRACT Biofilms are the leading cause of clinically acquired fungal infections and contribute to significantly high morbidity and mortality in immunocompromised and hospitalized patients. Candida biofilms exhibit increased resistance to currently available antifungal agents that contribute to persistent reoccurring infections and are driving efforts to identify novel fungicidal compounds. The natural product, occidiofungin, is an antifungal compound with demonstrated activity against hyphal morphogenesis in polymorphic Candida species. In this study, we use an in vitro static biofilm model to demonstrate the efficacy of occidiofungin against C. albicans and C. tropicalis at all stages of biofilm development, including inhibiting cell dispersal. Consistent with prior findings, we demonstrate that actin organization is altered following occidiofungin exposure to include loss of F-actin cables and accumulation of actin aggregates. Altogether, our results provide strong evidence of the antibiofilm activity of occidiofungin toward Candida biofilms and support its potential as a therapeutic for Candida infections. IMPORTANCE Candida are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of Candida virulence is the ability to form a biofilm. These structures are highly resistant to antifungal therapies and are often the cause of treatment failure. In this work, we evaluated the efficacy of the antifungal compound, occidiofungin, against Candida biofilms developed on a silicone surface. We demonstrate that occidiofungin eliminated cells at all stages of biofilm formation in a dose-dependent manner. Consistent with our understanding of occidiofungin bioactivity, we noted alterations to actin organization and cell morphology following antifungal exposure. Given the challenges associated with the treatment of biofilm-associated infections, occidiofungin exhibits potential as a therapeutic antifungal agent in the future.