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Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species
PURPOSE: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494979/ https://www.ncbi.nlm.nih.gov/pubmed/37700797 http://dx.doi.org/10.2147/IDR.S419646 |
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author | Li, Zhen Zhu, Bin Chen, Weiqin Hu, Jun Xue, Yingjun Yin, Hongmei Hu, Xiaobo Liu, Weiwei |
author_facet | Li, Zhen Zhu, Bin Chen, Weiqin Hu, Jun Xue, Yingjun Yin, Hongmei Hu, Xiaobo Liu, Weiwei |
author_sort | Li, Zhen |
collection | PubMed |
description | PURPOSE: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) and its synergistic effect with fluconazole (FLC) against NAC species, including C. tropicalis, C. parapsilosis complex, and C. glabrata. METHODS: The microdilution checkerboard assay and time-killing curves were performed to detect the antifungal efficiency. To examine the integrity of cell walls and membranes, calcofluor white stain and propidium iodide stain were used. The changes of intracellular ultrastructure in Candida cells after treatment were observed using transmission electron microscopy. Changes in cell viability with the autophagy inhibitor 3-MA were assessed by the XTT method. RESULTS: It was revealed that PAA alone is effective on C. tropicalis, C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis (MIC 8–128 µg/mL). Strong synergism against FLC-resistant C. tropicalis was observed (FICI 0.07–0.281), when PAA and FLC were combined. PAA had dose-dependently detrimental effects on C. tropicalis cell membranes. Moreover, increased vacuoles and autophagosome formation were found in C. tropicalis exposed to PAA. And the inhibitory effect of PAA against C. tropicalis can be relieved by autophagy inhibitor 3-MA in a certain concentration range. Ultrastructural alterations of C. tropicalis were more pronounced under the combination of PAA and FLC, including separation of the cell membrane from the cell wall, increased number of vacuoles, and degradation of organelles. CONCLUSION: These observations indicated that PAA and its combination with FLC could be a promising therapeutic candidate for treating infections caused by NAC species. |
format | Online Article Text |
id | pubmed-10494979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-104949792023-09-12 Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species Li, Zhen Zhu, Bin Chen, Weiqin Hu, Jun Xue, Yingjun Yin, Hongmei Hu, Xiaobo Liu, Weiwei Infect Drug Resist Original Research PURPOSE: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) and its synergistic effect with fluconazole (FLC) against NAC species, including C. tropicalis, C. parapsilosis complex, and C. glabrata. METHODS: The microdilution checkerboard assay and time-killing curves were performed to detect the antifungal efficiency. To examine the integrity of cell walls and membranes, calcofluor white stain and propidium iodide stain were used. The changes of intracellular ultrastructure in Candida cells after treatment were observed using transmission electron microscopy. Changes in cell viability with the autophagy inhibitor 3-MA were assessed by the XTT method. RESULTS: It was revealed that PAA alone is effective on C. tropicalis, C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis (MIC 8–128 µg/mL). Strong synergism against FLC-resistant C. tropicalis was observed (FICI 0.07–0.281), when PAA and FLC were combined. PAA had dose-dependently detrimental effects on C. tropicalis cell membranes. Moreover, increased vacuoles and autophagosome formation were found in C. tropicalis exposed to PAA. And the inhibitory effect of PAA against C. tropicalis can be relieved by autophagy inhibitor 3-MA in a certain concentration range. Ultrastructural alterations of C. tropicalis were more pronounced under the combination of PAA and FLC, including separation of the cell membrane from the cell wall, increased number of vacuoles, and degradation of organelles. CONCLUSION: These observations indicated that PAA and its combination with FLC could be a promising therapeutic candidate for treating infections caused by NAC species. Dove 2023-09-07 /pmc/articles/PMC10494979/ /pubmed/37700797 http://dx.doi.org/10.2147/IDR.S419646 Text en © 2023 Li et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Li, Zhen Zhu, Bin Chen, Weiqin Hu, Jun Xue, Yingjun Yin, Hongmei Hu, Xiaobo Liu, Weiwei Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title | Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title_full | Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title_fullStr | Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title_full_unstemmed | Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title_short | Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species |
title_sort | pseudolaric acid a: a promising antifungal agent against prevalent non-albicans candida species |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494979/ https://www.ncbi.nlm.nih.gov/pubmed/37700797 http://dx.doi.org/10.2147/IDR.S419646 |
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