Candidacidal effects of LL-37 and histatin 5

Objectives: Antimicrobial mechanisms of histatin 5 and the cathelicidin LL-37, two antimicrobial peptides present in human saliva, were studied in the oral yeast Candida albicans. Our goals were to elucidate whether both peptides cause damage to the C. albicans cell membrane and whether the damage caused was sufficient for candidacidal activity. Methods: Using confocal microscopy and freeze-fracture electron microscopy, the localization of the peptides was studied and the ultrastructural damage was evaluated. Using capillary electrophoresis and SDS-PAGE, peptide-induced leakage of essential cell components was evaluated. Results: Both LL-37 and histatin 5 kill the oral yeast C. albicans at comparable concentrations (approx. 1 ìM). LL-37 associated with the cell membrane of the yeast, whereas histatin 5 translocated over the cell membrane.Histatin caused little ultrastructural damage to the cell membrane, whereas the damage caused by LL-37 was much more severe. This is reflected by the fact that LL-37 caused leakage of small proteins, whereas histatin 5 did not. However, the peptides induce a similar loss of nucleotides, such as ATP, from C. albicans. As ATP is a vital energy carrier, loss of this compound necessarily leads to cell death. Conclusion: LL-37 and histatin 5 both exert their candidacidal activity by damage of the cell membrane. Whereas the ultrastructural defects caused by LL-37 and histatin 5 are very different, apparently they are sufficient for loss of vital compounds and subsequent cell death.