Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction
This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against <i>Candida</i> species. We evaluated the responses of nine reference species of <i>Candida</i> spp. and one hundred clinical isolates of <i>C. albicans</i&...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/13/2735 |
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| Summary: | This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against <i>Candida</i> species. We evaluated the responses of nine reference species of <i>Candida</i> spp. and one hundred clinical isolates of <i>C. albicans</i> to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive <i>Candida</i> species, <i>C. albicans</i> and <i>C. parapsilosis</i>. The frequency of spontaneous mutations occurring in these two <i>Candida</i> species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in <i>C. albicans</i> and <i>C. parapsilosis</i> cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10<sup>−5</sup> to 1.2 × 10<sup>−4</sup> per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti-<i>Candida</i> agent. |
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| ISSN: | 1420-3049 |