Antifungal Activity of Synthetic Scorpion Venom-Derived Peptide Analogues Against Candida albicans

Fungal infections are becoming a serious problem due to their high morbidity and mortality combined with the rise in drug resistance and dearth of new antimycotic drugs. The scorpion venom-derived peptide BmKn2, and its synthetic analogue Kn2–7, were previously observed to have antibacterial activity. These peptides and their d-amino acid analogues (dBmKn2 and dKn2–7) were tested for antifungal activity against drug resistant and clinical isolates of Candida albicans. In planktonic susceptibility studies, dKn2–7 had greater activity than the other three peptides against 6 out of 7 fungal strains, with no apparent correlation between drug resistance and minimum fungicidal concentrations (MFCs). Time kill experiments demonstrated that the fungicidal activity of dKn2–7 began within the first hour and killing rates were dose dependent at ≥ 1 × MFC. Against biofilms, the d-analogues were the most effective, while the l-analogues had low efficacy in most strains even at 10 times the planktonic MFC. Stability testing suggests that this increased efficacy of the d-analogues may be due to increased resistance to protease degradation compared to the l-analogues. Peptides were also assessed for mammalian cell toxicity. BmKn2 and dBmKn2 induced significant hemolysis at levels similar to their MFCs, whereas Kn2–7 and dKn2–7 caused hemolysis at 4–16 times their MFCs. The 50% inhibitory concentration (IC50) for dKn2–7 against murine fibroblasts was greater than or equal to the planktonic MFCs and biofilm IC50s for dKn2–7 in all C. albicans strains tested. These results support the potential for dKn2–7 to be further investigated as a novel antifungal therapeutic.