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High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections
文献类型：期刊论文
| 作者 | Zhang, LX ; Yan, KZ ; Zhang, Y ; Huang, R ; Bian, J ; Zheng, CS ; Sun, HX ; Chen, ZH ; Sun, N ; An, R ; Min, FG ; Zhao, WB ; Zhuo, Y ; You, JL ; Song, YJ ; Yu, ZY ; Liu, ZH ; Yang, KQ ; Gao, H ; Dai, HQ ; Zhang, XL ; Wang, J ; Fu, CZ ; Pei, G ; Liu, JT ; Zhang, S ; Goodfellow, M ; Jiang, YY ; Kuai, J ; Zhou, GC ; Chen, XP |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2007 |
| 卷号 | 104期号:11页码:4606-4611 |
| 关键词 | antifungal beauvericin ketoconazole |
| ISSN号 | 0027-8424 |
| 通讯作者 | zhanglixin@im.ac.cn |
| 中文摘要 | The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximate to 20,000 microbial extracts, 12 hits were identified with broadspectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy. |
| 学科主题 | Multidisciplinary Sciences |
| 收录类别 | SCI |
| 原文出处 | NATL ACAD SCIENCES |
| WOS记录号 | WOS:000244972700065 |
| 公开日期 | 2011-07-03 |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/4504]  |
| 专题 | 南海海洋研究所_中科院边缘海地质重点实验室 |
| 推荐引用方式 GB/T 7714 | Zhang, LX,Yan, KZ,Zhang, Y,et al. High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2007,104(11):4606-4611. |
| APA | Zhang, LX.,Yan, KZ.,Zhang, Y.,Huang, R.,Bian, J.,...&Chen, XP.(2007).High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,104(11),4606-4611. |
| MLA | Zhang, LX,et al."High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104.11(2007):4606-4611. |
入库方式： OAI收割
来源：南海海洋研究所
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