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Cell wall distraction and biofilm inhibition of marine Streptomyces derived angucycline in methicillin resistant Staphylococcus aureus
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-12-28 , DOI: 10.1016/j.micpath.2020.104712
Thankaraj Rajam Jabila Mary 1 , Rajaretinam Rajesh Kannan 1 , Appadurai Muthamil Iniyan 2 , Dasnamoorthy Ramachandran 1 , Samuel Gnana Prakash Vincent 2
Affiliation  

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 13488T. 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.



中文翻译:

耐甲氧西林金黄色葡萄球菌海洋链霉菌来源的环霉素对细胞壁的牵张和生物膜抑制

威胁生命的抗生素抗性病原体的出现及其相关的死亡率和发病率,使得来自不同生态环境的许多新抗生素成为必要。海洋海绵相关微生物有望提供此类抗菌化合物。在本研究中,我们报告了来自链霉菌属的安古环素抗生素8- O-甲基四丁霉素的抗菌和生物膜潜力。SBRK2从印度拉马斯瓦拉姆马纳尔湾的海洋海绵中分离出来。我们针对耐甲氧西林金黄色葡萄球菌的筛查计划来自海洋海绵相关放线菌的(MRSA)耐药性产生了生物活性菌株SBRK2。根据16S rRNA基因系统发育分析,该分离株与长链霉菌NBRC 13488 T密切相关。通过琼脂平板发酵,基于溶剂的萃取,TLC,HPLC纯化和基于LC-MS的重复复制的体外生产,揭示出该生物活性化合物为8- O-甲酰四霉素。鉴定出的针对MRSA的最小抑菌浓度为2μg/ mL。化合物8- O-甲基四菌霉素的亚抑制浓度可减少金黄色葡萄球菌的生物膜形成并增加了ATCC25923的细胞表面疏水性指数。对亚抑制浓度暴露的扫描电子显微镜观察显示膜表面起皱,轻微的细胞损伤表明该化合物的细胞壁分散特性。基于斑马鱼胚胎的毒性试验显示出100μg/ mL化合物的最大非致死浓度,表明安全指数呈正相关。Angucycline化合物8- O- metyltetrangomycin可能是开发针对抗药性病原体的生物膜药物的潜在候选者。

更新日期:2020-12-28
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