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

• Published in: Biomaterials science 2024-02, Vol.12 (4), p.99-13
• Main Authors: Qi, Gao-Feng, Cui, Xin, Gong, Xue-Feng, Cui, Xu, Xu, Huan-Ge, Liang, Qi-Lin, Zhang, Kuo, Sha, Xiao-Ling, Li, Litao, Wang, Gui-Yuan, Liang, Hong-Wen, Wang, Lei
• Format: Article
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d3bm01845h

Fungal infections contribute substantially to human morbidity and mortality. A 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 down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC 50 = 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection. The formation and transformation of antifungal peptide (AFP) nanoparticles (NPs) are presented. AFP self-assembles into NPs (i). AFP NPs target and bind to chitin (ii). AFP NPs transform into fibrous networks in solution (iii) and on the surface of fungal cells (iii′).