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开发红树内生真菌用于传染病药物发现。

Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery.

机构信息

Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.

Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA.

出版信息

Mar Drugs. 2018 Oct 10;16(10):376. doi: 10.3390/md16100376.

Abstract

There is an acute need for new and effective agents to treat infectious diseases. We conducted a screening program to assess the potential of mangrove-derived endophytic fungi as a source of new antibiotics. Fungi cultured in the presence and absence of small molecule epigenetic modulators were screened against and the ESKAPE panel of bacterial pathogens, as well as two eukaryotic infective agents, and . By comparison of bioactivity data among treatments and targets, trends became evident, such as the result that more than 60% of active extracts were revealed to be selective to a single target. Validating the technique of using small molecules to dysregulate secondary metabolite production pathways, nearly half (44%) of those fungi producing active extracts only did so following histone deacetylase inhibitory (HDACi) or DNA methyltransferase inhibitory (DNMTi) treatment.

摘要

目前非常需要新的、有效的药物来治疗传染病。我们开展了一个筛选项目,以评估红树林内生真菌作为新型抗生素来源的潜力。在存在和不存在小分子表观遗传调节剂的情况下培养真菌,并针对 和 ESKAPE 细菌病原体以及两种真核感染性病原体 和 进行筛选。通过对处理方法和目标之间的生物活性数据进行比较,出现了一些明显的趋势,例如,超过 60%的活性提取物被证明对单个目标具有选择性。该技术验证了使用小分子来扰乱次生代谢产物产生途径,近一半(44%)仅在组蛋白去乙酰化酶抑制剂(HDACi)或 DNA 甲基转移酶抑制剂(DNMTi)处理后才产生活性提取物的真菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6418/6212984/316e3004659a/marinedrugs-16-00376-g001.jpg

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