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海洋来源的放线菌蒽环类化合物对耐甲氧西林金黄色葡萄球菌的细胞壁分离和生物膜抑制作用。

Cell wall distraction and biofilm inhibition of marine Streptomyces derived angucycline in methicillin resistant Staphylococcus aureus.

机构信息

Infectious Disease Biology Lab, Centre for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai, 600119, Tamil Nadu, India.

Infectious Disease Biology Lab, Centre for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai, 600119, Tamil Nadu, India.

出版信息

Microb Pathog. 2021 Jan;150:104712. doi: 10.1016/j.micpath.2020.104712. Epub 2020 Dec 28.

Abstract

The emergence of life threatening antibiotic resistant pathogens and its associated mortality and morbidity necessitates many new antibiotics from diverse ecological habitats. Marine sponge associated microbes are promising to provide such antimicrobial compounds. In the present study, we report antibacterial and anti-biofilm potential of the angucycline antibiotic 8-O-metyltetrangomycin from Streptomyces sp. SBRK2 isolated from a marine sponge of Gulf of Mannar, Rameswaram, India. Our screening program to tackle methicillin-resistant Staphylococcus aureus (MRSA) drug resistance from marine sponge associated actinobacteria yielded the bioactive strain SBRK2. Based on 16S rRNA gene phylogenetic analysis the isolate was found to closely related with Streptomyces longispororuber NBRC 13488. In vitro production by agar plate fermentation, solvent based extraction, TLC, HPLC purification and LC-MS based de-replication revealed the bioactive compound as 8-O-metyltetrangomycin. The antibacterial minimum inhibitory concentrations against MRSA was identified as 2 μg/mL. Sub-inhibitory concentration of the compound 8-O-metyltetrangomycin reduced the biofilm formation of S. aureus ATCC25923 and increased the cell surface hydrophobicity index. Scanning electron microscopic observation of the sub-inhibitory concentration exposure revealed a wrinkled membrane surface and slight cellular damage shows the cell wall distracting property of the compound. Zebrafish embryo based toxicity assays exhibited 100 μg/mL of compound as maximal non-lethal concentration which had demonstrated the positive relationship in safety index. The angucycline compound 8-O-metyltetrangomycin could be a potential candidate for the development of anti-biofilm agents against drug resistant pathogens.

摘要

具有威胁生命的抗生素耐药性病原体的出现及其相关的死亡率和发病率,需要从各种生态环境中开发许多新的抗生素。来自海洋海绵共生微生物的抗生素具有提供此类抗菌化合物的潜力。在本研究中,我们报告了从印度拉梅斯瓦兰湾曼纳尔湾的海绵中分离出的链霉菌 SBRK2 产生的安古霉素类抗生素 8-O-甲基四氢霉素的抗菌和抗生物膜潜力。我们针对海洋海绵相关放线菌中耐甲氧西林金黄色葡萄球菌(MRSA)耐药性的筛选计划,筛选出了具有生物活性的 SBRK2 菌株。根据 16S rRNA 基因系统发育分析,该分离株与链霉菌 longispororuber NBRC 13488 密切相关。通过琼脂平板发酵、溶剂提取、TLC、HPLC 纯化和 LC-MS 去重复检测,发现该生物活性化合物为 8-O-甲基四氢霉素。该化合物对 MRSA 的最低抑菌浓度(MIC)为 2 μg/mL。亚抑菌浓度的 8-O-甲基四氢霉素可降低金黄色葡萄球菌 ATCC25923 的生物膜形成,并增加细胞表面疏水性指数。亚抑菌浓度暴露后的扫描电子显微镜观察显示,细胞膜表面出现皱纹,细胞轻微损伤,表明该化合物具有破坏细胞壁的特性。基于斑马鱼胚胎的毒性试验表明,化合物的 100μg/mL 浓度为最大非致死浓度,这表明安全性指数呈正相关。安古霉素类化合物 8-O-甲基四氢霉素可能是开发针对耐药病原体的抗生物膜药物的潜在候选药物。

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