Effects of histatin 5 and derived peptides on Candida albicans

Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active d...

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Bibliographic Details
Published in:Biochemical journal 2001-06, Vol.356 (Pt 2), p.361-368
Main Authors: Ruissen, A L, Groenink, J, Helmerhorst, E J, Walgreen-Weterings, E, Van't Hof, W, Veerman, E C, Nieuw Amerongen, A V
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antifungal Agents - chemistry
Antifungal Agents - pharmacokinetics
Antifungal Agents - pharmacology
Candida albicans
Candida albicans - drug effects
Candida albicans - metabolism
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Genetic Variation
histatin 5
Histatins
Membrane Potentials - drug effects
Microscopy, Confocal
Molecular Sequence Data
Salivary Proteins and Peptides - chemistry
Salivary Proteins and Peptides - genetics
Salivary Proteins and Peptides - pharmacology
Subcellular Fractions - metabolism
Vacuoles - drug effects
Vacuoles - metabolism
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Summary:Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active domain, with increased anti-microbial activity. dhvar4 has increased amphipathicity compared with histatin 5, whereas dhvar5 has amphipathicity comparable with that of histatin 5. All three peptides caused depolarization of the cytoplasmic and/or mitochondrial membrane, indicating membranolytic activity. For the variant peptides both depolarization and killing occurred at a faster rate. With FITC-labelled peptides, no association with the cytoplasmic membrane was observed, contradicting the formation of permanent transmembrane multimeric peptide pores. Instead, the peptides were internalized and act on internal membranes, as demonstrated with mitochondrion- and vacuole-specific markers. In comparison with histatin 5, the variant peptides showed a more destructive effect on mitochondria. Entry of the peptides and subsequent killing were dependent on the metabolic state of the cells. Blocking of the mitochondrial activity led to complete protection against histatin 5 activity, whereas that of dhvar4 was hardly affected and that of dhvar5 was affected only intermediately.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3560361