JAC Advance Access published online on April 8, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh181
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Oral Biology, University at Buffalo, The State
University of New York, Buffalo, NY 14214, USA
* Corresponding author. E-mail: lbobek{at}buffalo.edu.
Received 3 June 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
In vitro synergic antifungal effect
of MUC7 12-mer with
histatin-5 12-mer or miconazole
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