Abstract
Histatin 5 is a human basic salivary peptide with strong fungicidal properties in vitro. To elucidate the mechanism of action, the effect of histatin 5 on the viability of Candida albicans cells was studied in relation to its membrane perturbing properties. It was found that both the killing activity and the membrane perturbing activity, studied by the influx of a DNA-specific marker propidium iodide, were inhibited by high salt conditions and by metabolic inhibitors, like sodium azide. In addition, exposure to histatin 5 resulted in a loss of the mitochondrial transmembrane potential in situ, measured by the release of the potential-dependent distributional probe rhodamine 123. Localization studies using tetramethylrhodamine isothiocyanate-labeled histatin 5 or fluorescein isothiocyanate-labeled histatin 5 showed a granular intracellular distribution of the peptide, which co-localized with mitotracker orange, a permeant mitochondria-specific probe. Like the biological effects, uptake of labeled histatin 5 was inhibited by mitochondrial inhibitors and high salt conditions. Our data indicate that histatin 5 is internalized, and targets to the energized mitochondrion.
Highlights
It is generally recognized that basic peptides are important constituents of natural defense systems of most living organisms, including bacteria, plants, insects, and mammals
Killing and Permeabilization of C. albicans by Histatin 5—The effect of histatin 5 on the membrane integrity was studied by monitoring the influx of propidium iodide (PI), a DNA-staining fluorescent probe, into C. albicans cells
We addressed the mechanism of action of histatin 5, a basic amphipathic antifungal peptide from human saliva
Summary
It is generally recognized that basic peptides are important constituents of natural defense systems of most living organisms, including bacteria, plants, insects, and mammals. Examples of such antibiotic peptides are magainins, secreted by the skin of Xenopus laevis [1], defensins from the human neutrophils [2], and histatins from human saliva [3,4,5]. The susceptibility towards some of these peptides is controlled by the metabolic state of the target cell [8, 9] The mechanism underlying this phenomenon, is not understood. The direct association with the mitochondrion and the requirement of mitochondrial activity provide a new explanation for the energy-dependent activity of antimicrobial peptides against C. albicans
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