JAC Advance Access originally published online on April 8, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 750-758
© 2004 The British Society for Antimicrobial Chemotherapy
In vitro synergic antifungal effect of MUC7 12-mer with histatin-5 12-mer or miconazole
Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA
Received 3 June 2003; returned 18 August 2003; revised 12 January 2004; accepted 11 February 2004
Objectives: MUC7 12-mer (RKSYKCLHKRCR), a cationic peptide derived from human salivary MUC7 mucin, exhibits potent in vitro 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).
Methods: 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 Candida albicans and Cryptococcus neoformans 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 C. albicans and C. neoformans were determined by chequerboard assays and confirmed by killing assays. Toxicities of individual compounds were determined by haemolytic assays.
Results: 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). ED50 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 C. albicans; and 1.2 and 1.1 µM (or 1.9 and 1.7 mg/L), respectively, for C. neoformans. The killing of C. albicans and C. neoformans 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 C. neoformans, with a fractional inhibitory concentration index (FICI) of 0.37 and 0.25, respectively; and a slightly lower than synergic effect on C. albicans, 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.
Conclusions: This study suggests that MUC7 12-mer and Hsn5 12-mer peptides may be suitable candidates for use in combination antifungal therapy.
Keywords: antimicrobial peptides, salivary mucin, combination, chequerboard assay, haemolysis
* Corresponding author. Tel: +1-716-829-2465; Fax: +1-716-829-3942; E-mail: lbobek{at}buffalo.edu
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