Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Mar Drugs. 2020 Dec 24;19(1):7. doi: 10.3390/md19010007.
This study aims to isolate and identify the structure of antibacterial compounds having potent activity on methicillin-resistant (MRSA) from marine actinomycetes, and also to identify their mode of action. Lactoquinomycin A (LQM-A) (compound ) and its derivatives (-) were isolated from marine-derived strain MBTC38, and their structures were determined using extensive spectroscopic methods. These compounds showed potent antibacterial activities against Gram-positive bacteria, with MIC values of 0.06-4 μg/mL. However, the tested compounds exhibited weak inhibitory activity against Gram-negative bacteria, although they were effective against (MIC = 0.03-1 μg/mL). LQM-A exhibited the most significant inhibitory activity against methicillin-resistant (MRSA) (MIC = 0.25-0.5 μg/mL), with a low incidence of resistance. An in vivo dual-reporter assay designed to distinguish between compounds that inhibit translation and those that induce DNA damage was employed to assess the mode of action of LQM-A. LQM-A-induced DNA damage and did not inhibit protein synthesis. The gel mobility shift assay showed that LQM-A switched plasmid DNA from the supercoiled to relaxed form in a time- and concentration-dependent manner. These data suggest that LQM-A intercalated into double-stranded DNA and damaged DNA repair.
本研究旨在从海洋放线菌中分离和鉴定对耐甲氧西林金黄色葡萄球菌（MRSA）具有强效活性的抗菌化合物，并确定其作用模式。乳醌霉素 A（LQM-A）（化合物 ）及其衍生物（-）从海洋来源的 菌株 MBTC38 中分离得到，并通过广泛的光谱方法确定了它们的结构。这些化合物对革兰氏阳性菌表现出很强的抗菌活性，MIC 值为 0.06-4 μg/mL。然而，测试的化合物对革兰氏阴性菌的抑制活性较弱，尽管它们对 （MIC = 0.03-1 μg/mL）有效。LQM-A 对耐甲氧西林金黄色葡萄球菌（MRSA）（MIC = 0.25-0.5 μg/mL）的抑制活性最为显著，耐药发生率低。设计了一种双报告基因体内测定法，用于区分抑制翻译和诱导 DNA 损伤的化合物，以评估 LQM-A 的作用模式。LQM-A 诱导 DNA 损伤，不抑制蛋白质合成。凝胶迁移率变动分析表明，LQM-A 以时间和浓度依赖的方式将质粒 DNA 从超螺旋形式转变为松弛形式。这些数据表明，LQM-A 嵌入双链 DNA 并破坏 DNA 修复。
Zotero 插件
