Sphaeropsidin A Loaded in Liposomes to Reduce Its Cytotoxicity and Preserve Antifungal Activity Against <i>Candida auris</i>
<i>Candida</i> species constitute the most common cause of fungal infections in humans; the emergence of resistance and biofilm formation by <i>Candida</i> species further threaten the limited availability of antifungal agents. Over the past decade, <i>C</i>. <...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/24/5949 |
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| Summary: | <i>Candida</i> species constitute the most common cause of fungal infections in humans; the emergence of resistance and biofilm formation by <i>Candida</i> species further threaten the limited availability of antifungal agents. Over the past decade, <i>C</i>. <i>auris</i> has caused significant outbreaks worldwide and has emerged as a human pathogenic fungus that causes diseases ranging from superficial to life-threatening disseminated infections. Despite the recent advances in antifungal research, the mechanisms of drug resistance in <i>C. auris</i> remain poorly understood even as its ability to form biofilms poses a significant therapeutic challenge. The purpose of this research was to elucidate the fungal properties of Sphaeropsidin A (SphA), a secondary metabolite derived from <i>Diplodia</i> fungi, with a specific focus on its efficacy against <i>C. auris</i>. This study revealed that SphA and its liposomal encapsulated (SphA-L) form are fungistatic with time-kill kinetics highlighting their efficacy and significantly inhibited the formation of <i>C. auris</i> biofilms. Our investigation into the antifungal mechanism of this drug revealed notable alterations in ROS production and the disruption of the Candida cell cycle. Our findings show that SphA-L impairs key pathogenic traits of <i>C. auris</i>, such as its ability to adhere to human epithelial cell lines, while exhibiting no harmful effects on human cells, highlighting its potential as a future therapeutic agent. In <i>Caenorhabditis elegans</i> infection models, both ShpA and SphA-L displayed effective antifungal activity, significantly reducing the <i>C. auris</i> fungal load and improving nematode survival rates, underscoring their promise as antifungal candidates. Overall, the potent antifungal effects of SphA and SphA-L against <i>C. auris</i> encourage further research. |
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| ISSN: | 1420-3049 |