Antifungal activity of human salivary mucin-derived peptide, MUC 7 12-mer, in a murine model of oral candidiasis

Abstract

Previous studies have shown that peptides derived from the N-terminal region of the low molecular mass human salivary mucin, MUC7, possess potent in vitro cidal activity against Candida albicans and other medically important fungi. MUC7 12-mer (residues 40-51 of the parent MUC7) peptide, having the optimal size and a net charge of +6, was found to be anticandidal in human saliva (clarified and unclarified), and its candidacidal potency was found to be superior to that of histatin 5 12-mer (Hsn5 12-mer). We have, therefore, explored the candidacidal potency of MUC7 12-mer (l and d isomers) and Hsn5 12-mer peptides in vivo. In vitro killing assay was performed to establish killing activity of the peptides against C. albicans prior to in vivo experiments. A murine model of oral candidiasis that has the characteristics of oral thrush in humans was employed for the in vivo studies, based on a previous protocol. Upon candidal induction, antifungal treatment application using agents emulsified in Pluronic F127 was performed for six consecutive days. Amphotericin B and clotrimazole emulsified in the same delivery system were used as positive control drugs. Candidacidal efficacy was evaluated microbiologically and histopathologically. Results demonstrated a considerable reduction of fungal burden by the MUC7 12-mer peptides (l and d), comparable to control drugs, and this effect was statistically significant, unlike the effect seen with Hsn5 12-mer. Murine oral candidiasis model employed in this study is suitable to test the candidacidal agents employing Pluronic F127. In conclusion, MUC7 12-mer appears to be a promising candidate as an antifungal agent for oral candidiasis. Copyright Blackwell Munksgaard, 2006.