A self-assembling peptide inhibits the growth and function of fungi via wrapping strategy

Fungal infections contribute substantially to human morbidity and mortality. Particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows the morphological transformation of biphasic fungi, inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broadspectrum antifungal fluconazole, AFP achieved the comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibits the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy than fluconazole. In systemic candidiasis mice model, AFP showed similar efficacy with first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for the anti-fungal infection.