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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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2230009 |
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| _version_ | 1849418918026805248 |
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| author | Ying Li Chaoqun Chen Liu Cong Shanshan Mao Mingzhu Shan Zibing Han Jiayi Mao Zhiyu Xie Zuobin Zhu |
| author_facet | Ying Li Chaoqun Chen Liu Cong Shanshan Mao Mingzhu Shan Zibing Han Jiayi Mao Zhiyu Xie Zuobin Zhu |
| author_sort | Ying Li |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-89a8019186654fcab8c19b31fe968aec |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-89a8019186654fcab8c19b31fe968aec2025-08-20T03:32:18ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2230009Inhibitory effects of a maleimide compound on the virulence factors of Candida albicansYing Li0Chaoqun Chen1Liu Cong2Shanshan Mao3Mingzhu Shan4Zibing Han5Jiayi Mao6Zhiyu Xie7Zuobin Zhu8School of Medical Technology, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Technology, Xuzhou Medical University, Xuzhou, ChinaDepartment of Genetics, Xuzhou Medical University, Xuzhou, ChinaDepartment of Genetics, Xuzhou Medical University, Xuzhou, ChinaKey Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, College of Chemical and Materials Engineering, Xuchang University, Xuchang, ChinaDepartment of Genetics, Xuzhou Medical University, Xuzhou, ChinaCandidiasis 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.https://www.tandfonline.com/doi/10.1080/21505594.2023.2230009MPDCandida albicansvirulence factorshyphaecAMP |
| spellingShingle | Ying Li Chaoqun Chen Liu Cong Shanshan Mao Mingzhu Shan Zibing Han Jiayi Mao Zhiyu Xie Zuobin Zhu Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans Virulence MPD Candida albicans virulence factors hyphae cAMP |
| 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 | MPD Candida albicans virulence factors hyphae cAMP |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2230009 |
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