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Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Biological activity of Tat (47-58) peptide on human pathogenic fungi
Hyun Jun Jung1, Yoonkyung Park, Kyung-Soo Hahm
1Department of Microbiology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Puk-ku, Daegu 702-701, Republic of Korea.
Abstract:
Tat (47-58) peptide, a positively charged Arginine-rich peptide derived from HIV-1 regulatory protein Tat, is known for a peptidic delivery factor as a cell-penetrating peptide on mammalian cells. In this study, antifungal effect and its mode of action of Tat peptide were investigated on fungal cells. The results indicate that Tat peptide exhibits antifungal activity against pathogenic fungal cells without hemolytic effect on human erythrocytes. To understand the mechanism(s) of Tat peptide, the cellular distribution of the peptide was investigated. Tat peptide internalized in the fungal cells without any damage to cell membrane when examined using an artificial liposome (PC/cholesterol; 10:1, w/w). Moreover, flow cytometry analysis exhibited the uptake of Tat peptide by energy- and salt-independent pathway, and confocal scanning microscopy displayed that this peptide accumulated in the nucleus of fungal cells rapidly without any impediment by time or temperature, which generally influence on the viral infections. After penetration into the nuclear, the peptide affected the process of cell cycle of Candida albicans through the arrest at G1 phase.
Insights
The Tat (47-58) peptide shows antifungal activity against pathogenic fungi without harming human red blood cells. This cell-penetrating peptide enters fungal cells and halts their cell cycle progression in the G1 phase.
Area of Science:
- Mycology
- Biochemistry
- Molecular Biology
Background:
- The HIV-1 Tat (47-58) peptide is a cell-penetrating peptide (CPP) known for delivery into mammalian cells.
- Its potential as an antifungal agent and its mechanism of action in fungal cells remain largely unexplored.
Purpose of the Study:
- To investigate the antifungal effects of the Tat (47-58) peptide on pathogenic fungal cells.
- To elucidate the mechanism of action, including cellular uptake and intracellular localization.
Main Methods:
- Antifungal activity assays against pathogenic fungi.
- Hemolysis assays using human erythrocytes.
- Cellular uptake studies using artificial liposomes.
- Confocal scanning microscopy for intracellular localization.
- Flow cytometry for analyzing uptake pathways.
- Cell cycle analysis of Candida albicans.
Main Results:
- Tat (47-58) peptide demonstrated significant antifungal activity against pathogenic fungi.
- No hemolytic activity was observed on human erythrocytes, indicating safety.
- The peptide efficiently internalized into fungal cells without damaging the cell membrane.
- Uptake was independent of cellular energy and salt concentration.
- The peptide rapidly accumulated in the nucleus of fungal cells.
- Tat (47-58) peptide induced cell cycle arrest at the G1 phase in Candida albicans.
Conclusions:
- The Tat (47-58) peptide is a promising antifungal agent with a unique mechanism of action.
- Its ability to penetrate fungal cells and disrupt cell cycle progression warrants further investigation for therapeutic applications.

