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Updated: Jul 6, 2026

Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides
Slavena Vylkova1, Jianing N Sun, Mira Edgerton
1Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
Abstract:
A unifying theme common to the action of many cationic peptides that display lethal activities against microbial pathogens is their specific action at microbial membranes that results in selective loss of ions and small nucleotides-chiefly ATP. One model cationic peptide that induces non-lytic release of ATP from the fungal pathogen Candida albicans is salivary histatin 5 (Hst 5). The major characteristic of Hst 5-induced ATP release is that it occurs rapidly while cells are still metabolically active and have polarized membranes, thus precluding cell lysis as the means of release of ATP. Other cationic peptides that induce selective release of ATP from target microbes are lactoferricin, human neutrophil defensins, bactenecin, and cathelicidin peptides. The role of released extracellular ATP induced by cationic peptides is not known, but localized increases in extracellular ATP concentration may serve to potentiate cell killing, facilitate further peptide uptake, or function as an additional signal to activate the host innate immune system at the site of infection.
Insights
Cationic peptides, like salivary histatin 5, rapidly trigger non-lytic release of adenosine triphosphate (ATP) from fungal pathogens. This rapid release occurs while cells remain viable, suggesting novel antimicrobial mechanisms beyond cell death.
Area of Science:
- Microbiology
- Biochemistry
- Immunology
Background:
- Cationic peptides are crucial in antimicrobial defense, often targeting microbial membranes.
- Selective release of adenosine triphosphate (ATP) is a common mechanism observed with various antimicrobial peptides.
- Salivary histatin 5 (Hst 5) serves as a model peptide for studying non-lytic ATP release from Candida albicans.
Purpose of the Study:
- To investigate the non-lytic release of ATP induced by cationic peptides, specifically Hst 5, from Candida albicans.
- To characterize the conditions and implications of rapid, metabolically active ATP release.
- To explore the potential roles of extracellular ATP in microbial pathogenesis and host-pathogen interactions.
Main Methods:
- Utilized Candida albicans as a fungal model.
- Applied salivary histatin 5 (Hst 5) and other cationic peptides (lactoferricin, defensins, bactenecin, cathelicidins).
- Monitored rapid adenosine triphosphate (ATP) release from metabolically active and polarized cells, distinguishing it from cell lysis.
Main Results:
- Hst 5 rapidly induces non-lytic release of ATP from metabolically active Candida albicans.
- ATP release occurs independently of cell membrane permeabilization or lysis.
- Other cationic peptides also induce selective ATP release from microbial pathogens.
Conclusions:
- Cationic peptides can trigger rapid, non-lytic ATP release from microbial cells, indicating a mechanism distinct from membrane disruption.
- The extracellular ATP released may play roles in potentiating antimicrobial activity, peptide uptake, or signaling innate immune responses.
- Further research is needed to elucidate the precise functions of extracellular ATP in host-pathogen interactions.
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