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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2025-06-01
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| author | Ewa Lenarczyk Damian Oleksiak Monika Janeczko |
| author_facet | Ewa Lenarczyk Damian Oleksiak Monika Janeczko |
| author_sort | Ewa Lenarczyk |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fae5e6b4d6e44b4788523b0bf64f1366 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-fae5e6b4d6e44b4788523b0bf64f13662025-08-20T03:50:17ZengMDPI AGMolecules1420-30492025-06-013013273510.3390/molecules30132735Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence ReductionEwa Lenarczyk0Damian Oleksiak1Monika Janeczko2Doctoral School, The John Paul II Catholic University of Lublin, al. Racławickie 14, 20-950 Lublin, PolandExperimental Research Center, Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708 Lublin, PolandDepartment of Molecular Biology, Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708 Lublin, PolandThis 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.https://www.mdpi.com/1420-3049/30/13/2735antifungalshemolysisin vitro activitynucleosideszebrafish |
| spellingShingle | Ewa Lenarczyk Damian Oleksiak Monika Janeczko Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction Molecules antifungals hemolysis in vitro activity nucleosides zebrafish |
| title | Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction |
| title_full | Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction |
| title_fullStr | Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction |
| title_full_unstemmed | Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction |
| title_short | Antifungal Activity of 5-Fluorouridine Against <i>Candida albicans</i> and <i>Candida parapsilosis</i> Based on Virulence Reduction |
| title_sort | antifungal activity of 5 fluorouridine against i candida albicans i and i candida parapsilosis i based on virulence reduction |
| topic | antifungals hemolysis in vitro activity nucleosides zebrafish |
| url | https://www.mdpi.com/1420-3049/30/13/2735 |
| work_keys_str_mv | AT ewalenarczyk antifungalactivityof5fluorouridineagainsticandidaalbicansiandicandidaparapsilosisibasedonvirulencereduction AT damianoleksiak antifungalactivityof5fluorouridineagainsticandidaalbicansiandicandidaparapsilosisibasedonvirulencereduction AT monikajaneczko antifungalactivityof5fluorouridineagainsticandidaalbicansiandicandidaparapsilosisibasedonvirulencereduction |