In vitro antifungal activity and cytotoxicity of a novel membrane-active peptide

In the present study, we investigated the antifungal activity and cytotoxicity of a novel membrane-active peptide, KKVVFKVKFKK (MP). MP inhibited the growth of various pathogenic fungi isolated from patients and of fluconazole-resistant fungi at concentrations of 2 to 32 microg/ml. MP had potent fungicidal activity; the minimal fungicidal concentrations of the peptide were no more than fourfold greater than the MICs. Time course experiments of MP-induced killing of Candida albicans ATCC 36232 showed that the rate of killing was rapid and depended on the concentration of MP. MP had a strong synergism with other antifungal drugs; the fractional inhibitory concentration index values of MP with amphotericin B and fluconazole for C. albicans were 0.16 and 0.02, respectively. The 50% inhibitory concentrations of MP for NIH 3T3 and Jurkat cells were approximately 100 times higher than the MIC for C. albicans ATCC 36232, indicating that MP had high selectivity between the fungal and mammalian cells. These results suggest that MP has great advantages in the development of antifungal agents.