| Abstrakt: |
<it>Objectives</it>: MUC7 12-mer (RKSYKCLHKRCR), a cationic peptide derived from human salivary MUC7 mucin, exhibits potent <it>in vitro</it> antifungal activity, as determined by killing assays in phosphate buffer. In this study we examined the MUC7 12-mer antifungal activity alone or in combination with other antifungal agents in LYM medium (modified RPMI 1640). <it>Methods</it>: Antifungal activities of MUC7 12-mer and other compounds against several fungal strains were first measured by MIC and minimum fungicidal concentration (MFC) tests using broth microdilution assay. The viability of <it>Candida albicans</it> and <it>Cryptococcus neoformans</it> were also determined by killing assays and time kinetics of peptide-mediated killing. Antifungal activities of MUC7 12-mer in combination with other compounds [histatin-5 (Hsn5) 12-mer: AKRHHGYKRKFH, amphotericin B or miconazole] against <it>C. albicans</it> and <it>C. neoformans</it> were determined by chequerboard assays and confirmed by killing assays. Toxicities of individual compounds were determined by haemolytic assays. <it>Results</it>: MICs and MFCs of MUC7 12-mer ranged from 3.13 to 6.25 mg/L for most of the strains tested, and were, in most cases, comparable to those of amphotericin B and miconazole (0.78–6.25 mg/L). ED<inf>50</inf> values of MUC7 12-mer and Hsn5 12-mer were 7.1 and 7.4 µM (or 11.2 and 11.6 mg/L), respectively, for <it>C. albicans</it>; and 1.2 and 1.1 µM (or 1.9 and 1.7 mg/L), respectively, for <it>C. neoformans</it>. The killing of <it>C. albicans</it> and <it>C. neoformans</it> was achieved after 30 and 10 min exposure to the peptides, respectively. Combinations of MUC7 12-mer and Hsn5 12-mer, and of MUC7 12-mer and miconazole have a synergic antifungal effect on <it>C. neoformans</it>, with a fractional inhibitory concentration index (FICI) of 0.37 and 0.25, respectively; and a slightly lower than synergic effect on <it>C. albicans</it>, with a FICI of 0.63 and 0.56, respectively. In addition, using human erythrocytes, the two salivary peptides showed low levels of haemolytic activity. <it>Conclusions</it>: This study suggests that MUC7 12-mer and Hsn5 12-mer peptides may be suitable candidates for use in combination antifungal therapy. |
