Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery
Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery
复制标题
DOI：
10.3390/md16100376
复制
发表时间：
2018-10-01
期刊：
影响因子：
5.4
通讯作者：
Baker, Bill J.
中科院分区：
文献类型：
--
作者：
Demers, Danielle H.;Knestrick, Matthew A.;Baker, Bill J.
迫切需要新的和有效的药剂来治疗传染病。我们进行了一项筛选计划，以评估红树林内生真菌作为新抗生素来源的潜力。在存在和不存在小分子表观遗传调节剂的情况下培养的真菌针对结核分枝杆菌和ESKAPE细菌病原体组以及两种真核感染因子杜氏利什曼原虫和福氏耐格里原虫进行筛选。通过比较处理和靶标之间的生物活性数据，趋势变得明显，例如结果显示超过60%的活性提取物对单一靶标具有选择性。验证使用小分子失调次级代谢产物产生途径的技术，近一半（44%）的产生活性提取物的真菌仅在组蛋白脱乙酰酶抑制剂（HDACi）或DNA甲基转移酶抑制剂（DNMTi）处理后才这样做。
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 Mycobacterium tuberculosis and the ESKAPE panel of bacterial pathogens, as well as two eukaryotic infective agents, Leishmania donovani and Naegleria fowleri. 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.