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Published on: August 11, 2018
Histatins: antimicrobial peptides with therapeutic potential
1Medical Mycology Unit, Department of Biology, National Institute for Cellular Biotechnology, NUI Maynooth, Co. Kildare, Ireland. kevin.kavanagh@may.ie
Abstract:
Histatins are a group of antimicrobial peptides, found in the saliva of man and some higher primates, which possess antifungal properties. Histatins bind to a receptor on the fungal cell membrane and enter the cytoplasm where they target the mitochondrion. They induce the non-lytic loss of ATP from actively respiring cells, which can induce cell death. In addition, they have been shown to disrupt the cell cycle and lead to the generation of reactive oxygen species. Their mode of action is distinct from those exhibited by the conventional azole and polyene drugs, hence histatins may have applications in controlling drug-resistant fungal infections. The possibility of utilising histatins for the control of fungal infections of the oral cavity is being actively pursued with the antifungal properties of topical histatin preparations and histatin-impregnated denture acrylic being evaluated. Initial clinical studies are encouraging, having demonstrated the safety and efficacy of histatin preparations in blocking the adherence of the yeast Candida albicans to denture acrylic, retarding plaque formation and reducing the severity of gingivitis. Histatins may represent a new generation of antimicrobial compounds for the treatment of oral fungal infections and have the advantage, compared with conventional antifungal agents, of being a normal component of human saliva with no apparent adverse effects on host tissues and having a mode of action distinct to azole and polyene antifungals.
Insights
Histatins, antimicrobial peptides in human saliva, show potent antifungal activity by disrupting fungal cell mitochondria. These compounds offer a promising new strategy for treating drug-resistant oral fungal infections.
Area of Science:
- Biochemistry
- Microbiology
- Oral Medicine
Background:
- Histatins are salivary antimicrobial peptides with known antifungal properties.
- Conventional antifungal drugs like azoles and polyenes face challenges with drug resistance.
- Fungal infections, particularly in the oral cavity, require novel therapeutic approaches.
Purpose of the Study:
- To investigate the mechanism of action of histatins against fungal pathogens.
- To evaluate the potential of histatins as therapeutic agents for oral fungal infections.
- To assess the clinical efficacy and safety of histatin-based preparations.
Main Methods:
- Analysis of histatin interaction with fungal cell membranes and mitochondria.
- Assessment of ATP depletion, cell cycle disruption, and reactive oxygen species generation.
- Clinical evaluation of topical histatin preparations and histatin-impregnated denture acrylic.
Main Results:
- Histatins induce non-lytic ATP loss and cell death by targeting fungal mitochondria.
- Histatins disrupt the fungal cell cycle and generate reactive oxygen species.
- Clinical studies show histatin preparations are safe and effective in preventing Candida albicans adherence, reducing plaque, and improving gingivitis.
Conclusions:
- Histatins possess a unique mode of action distinct from conventional antifungals.
- Histatins represent a novel class of antimicrobial compounds for treating oral fungal infections.
- Histatin preparations demonstrate safety and efficacy, offering a promising alternative for managing drug-resistant fungal infections.
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