Antifungal activity of analogues of antimicrobial peptides isolated from bee venoms against vulvovaginal Candida spp.

Candida albicans is the main causative agent of vulvovaginal candidiasis (VVC), a common mycosis in women, relapses of which are difficult to manage due to biofilm formation. This study aimed at developing novel non-toxic compounds active against Candida spp. biofilms. We synthesised analogues of natural antifungal peptides LL-III (LL-III/43) and HAL-2 (peptide VIII) originally isolated from bee venoms and elucidated their structures by nuclear magnetic resonance spectroscopy. The haemolytic, cytotoxic, antifungal and anti-biofilm activities of LL-III/43 and peptide VIII were then tested. LL-III/43 and VIII showed moderate cytotoxicity to HUVEC-2 cells and had comparable inhibitory activity against C. albicans and non-albicans spp. The lowest minimum inhibitory concentration (MIC90) of LL-III/43 was observed towards Candida tropicalis (0.8 mu M). That was 8-fold lower than that of antimycotic amphotericin B. Both peptides can be used to inhibit Candida spp. biofilm formation. Biofilm inhibitory concentrations (BIC50) ranged from 0.9 to 58.6 mu M and biofilm eradication concentrations (BEC50) for almost all tested Candida spp. strains ranged from 12.8 to 200 mu M. Also proven were the peptides' abilities to reduce the area colonised by biofilms, inhibit hyphae formation and permeabilise cell membranes in biofilms. LL-III/43 and VIII are promising candidates for further development as therapeutics against VVC.