The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans
Abstract The increase in the number of immunocompromised individuals combined with the severity of fungal infections in the general population has contributed to a significant increase in opportunistic fungal infections, which are often associated with high mortality rates. Although effective, exist...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11018-6 |
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| author | Dimitris Tsiourvas Zili Sideratou Eleni Mavrogonatou Dimitris Kletsas Vicky Sophianopoulou Spiros Gerostathis |
| author_facet | Dimitris Tsiourvas Zili Sideratou Eleni Mavrogonatou Dimitris Kletsas Vicky Sophianopoulou Spiros Gerostathis |
| author_sort | Dimitris Tsiourvas |
| collection | DOAJ |
| description | Abstract The increase in the number of immunocompromised individuals combined with the severity of fungal infections in the general population has contributed to a significant increase in opportunistic fungal infections, which are often associated with high mortality rates. Although effective, existing antifungal drugs operate via a narrow range of mechanisms, leading to the rapid development of resistance and they primarily target growing host cells. Therefore, the need to develop next-generation antifungal agents that function via a broad range of mechanisms and/or target dormant/quiescent cells is highly important. In the present study, we investigated the characteristics and potential antifungal properties of a series of copper-chelated hyperbranched polyethyleneimines (PEI-Cu) with various molar ratios of Cu2+:primary amino groups of PEI (Cu: N), using the opportunistic pathogen Aspergillus nidulans as a model microorganism. Our results showed that PEI-Cu¼ and PEI–Cu¹⁄₁₆ complexes with Cu: N molar ratios of 1:4 and 1:16, respectively, retain the fungicidal activity of PEI. Cu2+ chelation seemed to delay the internalization of PEI-Cu, but they were found to exhibit apparent fungicidal activity on A. nidulans quiescent conidiospores while they affected hyphal growth rate, redox status and mitochondrial network morphology in A. nidulans germlings. In addition, no cytotoxic effects were observed on normal human skin fibroblasts at concentrations or incubation times that were entirely inhibitory for A. nidulans. Overall, our results suggest that the investigated PEI-Cu complexes are promising antifungals, and their underlying mechanism of action deserves further investigation, especially for use against drug-resistant quiescent fungal cells. |
| format | Article |
| id | doaj-art-fc9fe4c70e7c4ee6a3f6733f645387c0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-fc9fe4c70e7c4ee6a3f6733f645387c02025-08-20T03:42:38ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-11018-6The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulansDimitris Tsiourvas0Zili Sideratou1Eleni Mavrogonatou2Dimitris Kletsas3Vicky Sophianopoulou4Spiros Gerostathis5Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research “Demokritos”Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research “Demokritos”Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications (IBA), National Centre for Scientific Research “Demokritos”Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications (IBA), National Centre for Scientific Research “Demokritos”Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications (IBA), National Centre for Scientific Research “Demokritos”Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications (IBA), National Centre for Scientific Research “Demokritos”Abstract The increase in the number of immunocompromised individuals combined with the severity of fungal infections in the general population has contributed to a significant increase in opportunistic fungal infections, which are often associated with high mortality rates. Although effective, existing antifungal drugs operate via a narrow range of mechanisms, leading to the rapid development of resistance and they primarily target growing host cells. Therefore, the need to develop next-generation antifungal agents that function via a broad range of mechanisms and/or target dormant/quiescent cells is highly important. In the present study, we investigated the characteristics and potential antifungal properties of a series of copper-chelated hyperbranched polyethyleneimines (PEI-Cu) with various molar ratios of Cu2+:primary amino groups of PEI (Cu: N), using the opportunistic pathogen Aspergillus nidulans as a model microorganism. Our results showed that PEI-Cu¼ and PEI–Cu¹⁄₁₆ complexes with Cu: N molar ratios of 1:4 and 1:16, respectively, retain the fungicidal activity of PEI. Cu2+ chelation seemed to delay the internalization of PEI-Cu, but they were found to exhibit apparent fungicidal activity on A. nidulans quiescent conidiospores while they affected hyphal growth rate, redox status and mitochondrial network morphology in A. nidulans germlings. In addition, no cytotoxic effects were observed on normal human skin fibroblasts at concentrations or incubation times that were entirely inhibitory for A. nidulans. Overall, our results suggest that the investigated PEI-Cu complexes are promising antifungals, and their underlying mechanism of action deserves further investigation, especially for use against drug-resistant quiescent fungal cells.https://doi.org/10.1038/s41598-025-11018-6 |
| spellingShingle | Dimitris Tsiourvas Zili Sideratou Eleni Mavrogonatou Dimitris Kletsas Vicky Sophianopoulou Spiros Gerostathis The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans Scientific Reports |
| title | The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans |
| title_full | The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans |
| title_fullStr | The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans |
| title_full_unstemmed | The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans |
| title_short | The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans |
| title_sort | effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of aspergillus nidulans |
| url | https://doi.org/10.1038/s41598-025-11018-6 |
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