Jayathilaka E H T Thulshan, Rajapaksha Dinusha C, Nikapitiya Chamilani, De Zoysa Mahanama, Whang Ilson
College of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 34134, Korea.
National Marine Biodiversity Institute of Korea (MABIK), 75, Jangsan-ro 101 beon-gil, Janghang-eup, Seochun-gun, Chungchungnam-do 33662, Korea.
Int J Mol Sci. 2021 May 19;22(10):5353. doi: 10.3390/ijms22105353.
is a serious nosocomial pathogen with multiple drug resistance (MDR), the control of which has become challenging due to the currently used antibiotics. Our main objective in this study is to determine the antibacterial and antibiofilm activities of the antimicrobial peptide, Octominin, against MDR and derive its possible modes of actions. Octominin showed significant bactericidal effects at a low minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of 5 and 10 µg/mL, respectively. Time-kill kinetic analysis and bacterial viability tests revealed that Octominin showed a concentration-dependent antibacterial activity. Field-emission scanning electron microscopy (FE-SEM) analysis revealed that Octominin treatment altered the morphology and membrane structure of . Propidium iodide (PI) and reactive oxygen species (ROS) generation assays showed that Octominin increased the membrane permeability and ROS generation in , thereby causing bacterial cell death. Further, a lipopolysaccharides (LPS) binding assay showed an Octominin concentration-dependent LPS neutralization ability. Biofilm formation inhibition and eradication assays further revealed that Octominin inhibited biofilm formation and showed a high biofilm eradication activity against . Furthermore, up to a concentration of 100 µg/mL, Octominin caused no hemolysis and cell viability changes in mammalian cells. An in vivo study in zebrafish showed that the Octominin-treated group had a significantly higher relative percentage survival (54.1%) than the untreated group (16.6%). Additionally, a reduced bacterial load and fewer alterations in histological analysis confirmed the successful control of by Octominin in vivo. Collectively, these data suggest that Octominin exhibits significant antibacterial and antibiofilm activities against the multidrug-resistant , and this AMP can be developed further as a potent AMP for the control of antibiotic resistance.
是一种具有多重耐药性（MDR）的严重医院病原体，由于目前使用的抗生素，对其控制已变得具有挑战性。本研究的主要目的是确定抗菌肽Octominin对多重耐药菌的抗菌和抗生物膜活性，并推导其可能的作用模式。Octominin在低最低抑菌浓度（MIC）和最低杀菌浓度（MBC）分别为5和10μg/mL时显示出显著的杀菌效果。时间-杀菌动力学分析和细菌活力测试表明，Octominin显示出浓度依赖性抗菌活性。场发射扫描电子显微镜（FE-SEM）分析表明，Octominin处理改变了（此处原文缺失相关细菌名称）的形态和膜结构。碘化丙啶（PI）和活性氧（ROS）生成测定表明，Octominin增加了（此处原文缺失相关细菌名称）的膜通透性和ROS生成，从而导致细菌细胞死亡。此外，脂多糖（LPS）结合测定显示Octominin具有浓度依赖性LPS中和能力。生物膜形成抑制和根除测定进一步表明，Octominin抑制生物膜形成，并对（此处原文缺失相关细菌名称）显示出高生物膜根除活性。此外，在浓度高达100μg/mL时，Octominin在哺乳动物细胞中未引起溶血和细胞活力变化。斑马鱼体内研究表明，Octominin处理组的相对存活率（54.1%）显著高于未处理组（16.6%）。此外，细菌载量的减少和组织学分析中较少的改变证实了Octominin在体内成功控制了（此处原文缺失相关细菌名称）。总体而言，这些数据表明Octominin对多重耐药的（此处原文缺失相关细菌名称）表现出显著的抗菌和抗生物膜活性，并且这种抗菌肽可以进一步开发成为控制抗生素耐药性的有效抗菌肽。
