Rationalisation of antifungal properties of α-helical pore-forming peptide, mastoparan B

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionThis research was funded by the Singapore Ministry of Health’s National Medical Research Council (NMRC) under its Centre Grant Program—Optimization of Core Platform Technologies for Ocular Research (INCEPTOR)-NMRC/CG/M010/2017, Open Fund—Large Collaborative Grant (OFLCG18May-0028), the SingHealth Foundation (SHF/FG663P/2017) and the Agency for Science, Technology and Research (A*STAR) under its Wound Care Innovation for the Tropics (WCIT) Industry Alignment Fund Pre-Positioning (IAF-PP) grant (H17/01/a0/0K9). The work was also supported by the Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 grants (2020-T1-001-062 and R-148-000-309-114). The APC was funded by R1875/3/2022