Antifungal activity of human salivary mucin‐derived peptide, MUC7 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.

Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

“…This suggests that MUC7 12-mer peptide is active for oral candidiasis in oral physiological conditions. This is consistent with the observation of our previous study using mouse model of oral candidiasis in vivo [ 27 ]. The other reported NaCl-resistant peptides include clavanins (histidine-rich, amidated alpha-helical antimicrobial peptides) [ 28 ], CP26, CP29, CEME, CEMA (the analogues based on the insect cecropin-bee melittin hybrid peptide) [ 29 ], P18 (KWKLFKKIPKFLHLAKKF, an alpha-helical antimicrobial peptide) [ 30 ], cathelicidin CAP18, SMAP29 [ 31 ], and modified forms of LL-37, such as pentamide-37 [ 32 ].…”

Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces

“…In the mucous lining, additional protection is given against potential invaders by bactericidal components such as resistin-like molecule β and zymogen granulae protein 16 that are secreted from Goblet cells [ 21 , 22 ], as well as by antifungal peptides such as histatins and MUC7 12-mer [ 23 , 24 ]. In the small intestine, Paneth cells release bactericidal defensins, lysozyme, and cryptdins into the gut lumen [ 25 ].…”

Biopolymeric Mucin and Synthetic Polymer Analogs: Their Structure, Function and Role in Biomedical Applications

“…In xerostomic patients, there is an increased susceptibility to microbial colonization leading to oral infections (e.g., candidiasis) [ 52 , 54 , 55 ]. For instance, mucin contains antifungal peptides (e.g., histatins, MUC7 12-mer) [ 56 , 57 , 58 , 59 ], which play a key role in inhibiting candidiasis, a prevalent fungal infection that results from Candida albicans. Nearly 95% incidence rate of candidiasis was reported among patients with acquired immunodeficiency syndrome (AIDS) [ 60 ].…”