Antimicrobial activity of human salivary mucin-derived peptides.

We investigated: a) relationships between molecular properties and antimicrobial functions of MUC7 peptides, b) effects of host physiological factors on the antimicrobial activity of MUC7 peptides, c) enhancement of antifungal activity by combination of MUC7 peptides with EDTA or other agents, d) antibacterial activity of MUC7 peptides against dental biofilm and e) toxicity of the MUC7 peptides. In conclusion: MUC7 12-mer peptide is a potential candidate for the development of a novel antifungal therapeutic agent. This peptide is not sensitive to mono- or divalent cations except for calcium ions at oral physiological-like concentrations. The peptide is thermo-stable and possesses a broad optimal pH value that ranges from neutral to slightly alkaline. MUC7 12-mer is less susceptible to degradation by salivary proteases derived from oral bacteria, compared to other CAMPs. MUC7 12-mer with D-amino acid substitution is resistant to proteolysis while also retaining an effective antifungal activity. Protease inhibitors cocktails and EDTA enhance the activity of MUC7 12-mer. The combination MUC7 12-mer with histatin5 12-mer or MUC7 12-mer with miconazole could potentially enhance the efficacy of antifungal therapy. MUC7 peptides have preferential antibacterial activity against S. mutans and may potentially be used as promising selective anti-dental plaque agents for the prevention of a cariogenic biofilm. MUC7 peptides are not toxic to mammalian cells under normal physiological conditions. The findings presented in the thesis strongly suggest that MUC7 12-mer peptide could potentially be used as a promising agent for the development of novel drugs that control oral microbial infection. The therapeutic efficacy may potentially be enhanced by the use of MUC7 12-mer D-enantiomers as well as the combinations of MUC7 12-mer and EDTA or other antimicrobial agents