Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic.
FEMS Yeast Res. 2019 May 1;19(3). doi: 10.1093/femsyr/foz013.
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 µM). That was 8-fold lower than that of antimycotic amphotericin B. Both peptides can be used to inhibit Candida spp. bio film f ormation. Biofilm inhibitory concentrations (BIC50) ranged from 0.9 to 58.6 µM and biofilm eradication concentrations (BEC50) for almost all tested Candida spp. strains ranged from 12.8 to 200 µM. Als o pro ven were the peptides' abilities to reduce the area colonised by biofilms , inhibit hyphae formation and permeabilise cell membranes in biofil ms . LL-III/43 and VIII are promising candidates for further development as therapeutics against VVC.
白色念珠菌是外阴阴道念珠菌病（VVC）的主要病原体，VVC 是一种常见的女性真菌感染，由于生物膜的形成，其复发难以治疗。本研究旨在开发针对念珠菌生物膜的新型无毒化合物。我们合成了天然抗真菌肽 LL-III（LL-III/43）和 HAL-2（肽 VIII）的类似物，这些肽最初是从蜂毒中分离出来的，并通过核磁共振波谱法阐明了它们的结构。然后测试了 LL-III/43 和肽 VIII 的溶血、细胞毒性、抗真菌和抗生物膜活性。LL-III/43 和 VIII 对 HUVEC-2 细胞具有中等细胞毒性，对白色念珠菌和非白色念珠菌 spp. 的抑制活性相当。LL-III/43 对热带念珠菌的最低最小抑菌浓度（MIC90）为 0.8µM，比抗真菌药物两性霉素 B 低 8 倍。两种肽都可以用来抑制念珠菌生物膜的形成。生物膜抑制浓度（BIC50）范围为 0.9 至 58.6µM，几乎所有测试的念珠菌 spp. 菌株的生物膜根除浓度（BEC50）范围为 12.8 至 200µM。还证明了这些肽能够减少生物膜定植的面积、抑制菌丝形成和使生物膜中的细胞膜通透性增加的能力。LL-III/43 和 VIII 是进一步开发治疗 VVC 药物的有前途的候选物。
