A semisynthetic borrelidin analogue BN-3b exerts potent antifungal activity against Candida albicans through ROS-mediated oxidative damage
| Autor: | Bixuan Cao, Yu Mu, Caijuan Hu, Xueshi Huang, Li Han, Peipei Guan, Hao Su, Xiaodan Qu |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antifungal Agents Virulence Factors 030106 microbiology Hyphae Down-Regulation Virulence lcsh:Medicine Endogeny Mechanism of action Article Microbiology Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate In vivo Malondialdehyde Target identification Candida albicans Animals lcsh:Science chemistry.chemical_classification Reactive oxygen species Multidisciplinary Glutathione Disulfide biology Chemistry lcsh:R Candidiasis Glutathione biology.organism_classification Corpus albicans Disease Models Animal 030104 developmental biology lcsh:Q Fatty Alcohols Reactive Oxygen Species Invasive Fungal Infections |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-61681-0 |
| Popis: | In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis. |
| Databáze: | OpenAIRE |
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