Journal Article

<i>In vitro</i> synergic antifungal effect of MUC7 12-mer with histatin-5 12-mer or miconazole

Guo-Xian Wei and Libuse A. Bobek

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 5, pages 750-758
Published in print May 2004 | ISSN: 0305-7453
Published online May 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh181
In vitro synergic antifungal effect of MUC7 12-mer with  histatin-5 12-mer or miconazole

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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: Keywords: antimicrobial peptides, salivary mucin, combination, chequerboard assay, haemolysis

Journal Article.  7268 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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