Candida albicans infections are a global health thread and challenge healthcare environments due to acquired resistances against prominent antifungals like amphotericin B and fluconazole, which additionally have severe adverse effects. The peptide Pom-1 originally isolated from the freshwater mollusk Pomacea poeyana, and its derivatives Pom-1 A-F have proven their potential against biofilms of clinical C. albicans isolates and were suspected to act without candidolytic pore-formation. Here, Pom-1 and its derivatives were shown to act as neutralizing antimicrobial peptides (nAMPs) inhibiting cell-cell interactions and hence biofilm formation. Combining Pom-1 nAMPs with fluconazole and amphotericin B restored their efficacy against resistant C. albicans isolates. Addition of Pom-1 nAMPs allowed to reduce required concentrations to 10-50percent-flag-change below their described effective therapeutic doses. This opens doors not only to mitigate adverse effects of fluconazole and amphotericin B therapies, but also towards novel combination therapies against C. albicans as a severe re-emerging pathogen.
