In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus
文献类型：期刊论文
| 作者 | Chen, Peiying6; Yang, Jing6; Jin, Yuanling6; Lu, Chujie2,6; Feng, Zhenzhen6; Gao, Fei6; Chen, Yuan6; Wang, Fuling6; Shang, Zhuo1; Lin, Wei3,4,5,6 |
| 刊名 | JOURNAL DE MYCOLOGIE MEDICALE
 |
| 出版日期 | 2023-05-01 |
| 卷号 | 33期号:2页码:101381 |
| 关键词 | Auranofin Thioredoxin reductase Itraconazole Aspergillus Antifungal drug |
| DOI | 10.1016/j.mycmed.2023.101381 |
| 文献子类 | Article |
| 英文摘要 | Background: Infections caused by azole-resistant Aspergillus are a rising public health threat with high mortality rates, high treatment costs and limited available antifungals, indicating an urgent need for new antifungals or strategies. Our aim was to investigate antifungal and antibiofilm activities of auranofin, an FDAapproved anti-antirheumatic drug. Methods: Fungal susceptibility testing for auranofin was carried out by the broth-based microdilution methods. Cell viability treated by auranofin was tested by resazurin dye testing. The synergistic effect of auranofin and antifungal drugs was evaluated using checkboard assay. The inhibitory of biofilms were measured by crystal violet staining. Gene expression level analysis and enzyme activity was investigated with qRT-PCR analysis and DTNB assay. The key amino acid residues in the binding of auranofin with A. fumigatus thioredoxin reductase (AfTrxR) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays. Results: Auranofin has fungicidal activity and in vitro antifungal spectrum including Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Aspergillus niger, even itraconazole (ITC)-resistant A. fumigatus. Additionally, it has antibiofilm activities against ITC-resistant A. fumigatus by reducing the expression level of SomA and MedA. Moreover, we discovered a synergistic effect of auranofin and ITC or amphotericin B against ITCresistant A. fumigatus. Auranofin downregulated the gene transcription of AfTrxR, and strongly inhibited the enzyme activity of AfTrxR through interacting with residues C145 and C148. Conclusions: Auranofin has fungicidal and antibiofilm activities in Aspergillus spp. and is also a potentiator of ITC or amphotericin B in vitro. |
| WOS关键词 | THIOREDOXIN REDUCTASE |
| WOS研究方向 | Mycology |
| 语种 | 英语 |
| 出版者 | MASSON EDITEUR |
| WOS记录号 | WOS:000981402100001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309649]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Peiying; Lin, Wei |
| 作者单位 | 1.Shandong Univ, Sch Pharmaceut Sci, Jinan 250012, Peoples R China 2.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China; 3.Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Nanjing 210023, Peoples R China; 4.Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, Nanjing 210023, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Nanjing 210023, Peoples R China; 6.Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Dept Pathogen Biol, Nanjing, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Peiying,Yang, Jing,Jin, Yuanling,et al. In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus[J]. JOURNAL DE MYCOLOGIE MEDICALE,2023,33(2):101381. |
| APA | Chen, Peiying.,Yang, Jing.,Jin, Yuanling.,Lu, Chujie.,Feng, Zhenzhen.,...&Lin, Wei.(2023).In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus.JOURNAL DE MYCOLOGIE MEDICALE,33(2),101381. |
| MLA | Chen, Peiying,et al."In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus".JOURNAL DE MYCOLOGIE MEDICALE 33.2(2023):101381. |
入库方式： OAI收割
来源：上海药物研究所
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