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Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans

Candidiasis caused by Candida albicans infection has long been a serious human health problem. The pathogenicity of C. albicans is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compoun...

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Autores principales: Li, Ying, Chen, Chaoqun, Cong, Liu, Mao, Shanshan, Shan, Mingzhu, Han, Zibing, Mao, Jiayi, Xie, Zhiyu, Zhu, Zuobin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321171/
https://www.ncbi.nlm.nih.gov/pubmed/37367101
http://dx.doi.org/10.1080/21505594.2023.2230009
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author Li, Ying
Chen, Chaoqun
Cong, Liu
Mao, Shanshan
Shan, Mingzhu
Han, Zibing
Mao, Jiayi
Xie, Zhiyu
Zhu, Zuobin
author_facet Li, Ying
Chen, Chaoqun
Cong, Liu
Mao, Shanshan
Shan, Mingzhu
Han, Zibing
Mao, Jiayi
Xie, Zhiyu
Zhu, Zuobin
author_sort Li, Ying
collection PubMed
description Candidiasis caused by Candida albicans infection has long been a serious human health problem. The pathogenicity of C. albicans is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compound [1-(4-methoxyphenyl)-1hydro-pyrrole-2,5-dione, MPD] that exerts effective anti-virulence activity. It could inhibit the process of adhesion, filamentation, and biofilm formation in C. albicans. In addition, it exhibited low cytotoxicity, hemolytic activity, and drug resistance development. Moreover, in Galleria mellonella-C. albicans (in vivo) infection model, the survival time of infected larvae was significantly prolonged under the treatment of MPD. Further, mechanism research revealed that MPD increased farnesol secretion by upregulating the expression of Dpp3. The increased farnesol inhibited the activity of Cdc35, which then decreased the intracellular cAMP content resulting in the inhibition of virulence factors via the Ras1-cAMP-Efg1 pathway. In all, this study evaluated the inhibitory effect of MPD on various virulence factors of C. albicans and identified the underlying mechanisms. This suggests a potential application of MPD to overcome fungal infections in clinics.
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spelling pubmed-103211712023-07-06 Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans Li, Ying Chen, Chaoqun Cong, Liu Mao, Shanshan Shan, Mingzhu Han, Zibing Mao, Jiayi Xie, Zhiyu Zhu, Zuobin Virulence Research Paper Candidiasis caused by Candida albicans infection has long been a serious human health problem. The pathogenicity of C. albicans is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compound [1-(4-methoxyphenyl)-1hydro-pyrrole-2,5-dione, MPD] that exerts effective anti-virulence activity. It could inhibit the process of adhesion, filamentation, and biofilm formation in C. albicans. In addition, it exhibited low cytotoxicity, hemolytic activity, and drug resistance development. Moreover, in Galleria mellonella-C. albicans (in vivo) infection model, the survival time of infected larvae was significantly prolonged under the treatment of MPD. Further, mechanism research revealed that MPD increased farnesol secretion by upregulating the expression of Dpp3. The increased farnesol inhibited the activity of Cdc35, which then decreased the intracellular cAMP content resulting in the inhibition of virulence factors via the Ras1-cAMP-Efg1 pathway. In all, this study evaluated the inhibitory effect of MPD on various virulence factors of C. albicans and identified the underlying mechanisms. This suggests a potential application of MPD to overcome fungal infections in clinics. Taylor & Francis 2023-07-02 /pmc/articles/PMC10321171/ /pubmed/37367101 http://dx.doi.org/10.1080/21505594.2023.2230009 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Li, Ying
Chen, Chaoqun
Cong, Liu
Mao, Shanshan
Shan, Mingzhu
Han, Zibing
Mao, Jiayi
Xie, Zhiyu
Zhu, Zuobin
Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title_full Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title_fullStr Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title_full_unstemmed Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title_short Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans
title_sort inhibitory effects of a maleimide compound on the virulence factors of candida albicans
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321171/
https://www.ncbi.nlm.nih.gov/pubmed/37367101
http://dx.doi.org/10.1080/21505594.2023.2230009
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