Newly Discovered Antimicrobial Peptide Scyampcin44-63 from Scylla paramamosain Exhibits a Multitargeted Candidacidal Mechanism In Vitro and Is Effective in a Murine Model of Vaginal Candidiasis.

ABSTRACT

The emergence of azole-resistant and biofilm-forming Candida spp. contributes to the constantly increasing incidence of vulvovaginal candidiasis. It is imperative to explore new antifungal drugs or potential substituents, such as antimicrobial peptides, to alleviate the serious crisis caused by resistant fungi. In this study, a novel antimicrobial peptide named Scyampcin44-63 was identified in the mud crab Scylla paramamosain. Scyampcin44-63 exhibited broad-spectrum antimicrobial activity against bacteria and fungi, was particularly effective against planktonic and biofilm cells of Candida albicans, and exhibited no cytotoxicity to mammalian cells (HaCaT and RAW264.7) or mouse erythrocytes. Transcriptomic analysis revealed four potential candidacidal modes of Scyampcin44-63, including promotion of apoptosis and autophagy and inhibition of ergosterol biosynthesis and the cell cycle. Further study showed that Scyampcin44-63 caused damage to the plasma membrane and induced apoptosis and cell cycle arrest at G2/M in C. albicans. Scanning and transmission electron microscopy demonstrated that Scyampcin44-63-treated C. albicans cells were deformed with vacuolar expansion and destruction of organelles. In addition, C. albicans cells pretreated with the autophagy inhibitor 3-methyladenine significantly delayed the candidacidal effect of Scyampcin44-63, suggesting that Scyampcin44-63 might contribute to autophagic cell death. In a murine model of vulvovaginal candidiasis, the fungal burden of vaginal lavage was significantly decreased after treatment with Scyampcin44-63.