Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, China.
Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China.
Mar Drugs. 2020 Dec 17;18(12):650. doi: 10.3390/md18120650.
can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against were 1.29-3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 μg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by , superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against infections.
可导致鱼类和人类致命的胃肠/肠道疾病。抗生素的过度使用导致了抗生素耐药性和环境污染，这凸显了寻找新的抗菌剂的必要性。在这项研究中，海洋肽-N6 在其 C 末端被酰胺化以生成 N6NH2。体外和体内评估了 N6 和 N6NH2 对 的抗菌活性；还测定了它们的稳定性、毒性和作用模式。N6 和 N6NH2 对 的最小抑菌浓度 (MIC) 分别为 1.29-3.2 μM。N6 和 N6NH2 通过破坏 和结合脂多糖 (LPS) 和基因组 DNA 来杀死细菌。与 N6 相比，N6NH2 提高了对胰蛋白酶的稳定性，降低了溶血（在 256 μg/mL 浓度下降低了 0.19%），并增强了穿透细菌内外膜的能力。在由 引起的鱼类腹膜炎模型中，优于诺氟沙星，N6NH2 提高了鱼类的存活率，降低了器官上的细菌负荷，减轻了器官损伤，并调节了肝肾功能的免疫。这些数据表明，海洋肽 N6NH2 可能是一种新型抗菌剂治疗 感染的候选药物。
