Zhang Shuang, Yang Na, Mao Ruoyu, Hao Ya, Teng Da, Wang Jianhua
Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, China.
Innovative Team of Antimicrobial Peptides and Alternatives to Antibiotics, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Antibiotics (Basel). 2024 Apr 8;13(4):341. doi: 10.3390/antibiotics13040341.
is an opportunistic pathogen commonly found in canines, and has garnered escalating interest due to its potential for zoonotic transmission and increasing antimicrobial resistance. However, the excessive use of antibiotics and the characteristic of forming biofilms make treatment challenging. In this study, the in vivo and in vitro antimicrobial activity and mechanisms of action of NZ2114, a plectasin-derived peptide, against were investigated. NZ2114 exhibited potent antibacterial activity towards (minimum inhibitory concentration, MIC = 0.23 μM) with a lower probability of inducing drug-resistant mutations and efficient bactericidal action, which was superior to those of mopirucin (MIC = 0.25-0.5 μM) and lincomycin (MIC = 4.34-69.41 μM). The results of electron microscopy and flow cytometry showed that NZ2114 disrupted cell membrane, resulting in cellular content leakage, cytoplasmic membrane shrinkage, and, eventually, cell death. The intracellular ROS activity and Alamar Blue detection showed that NZ2114 interferes with intracellular metabolic processes. In addition, NZ2114 effectively inhibits biofilm formation, and confocal laser scanning microscopy further revealed its antibacterial and anti-biofilm activity (biofilm thickness reduced to 6.90-17.70 μm). The in vivo therapy of NZ2114 in a mouse pyoderma model showed that it was better than lincomycin in effectively decreasing the number of skin bacteria, alleviating histological damage, and reducing the skin damage area. These results demonstrated that NZ2114 may be a promising antibacterial candidate against infections.
是一种常见于犬类的机会性致病菌，由于其具有人畜共患病传播潜力和日益增加的抗菌药物耐药性，已引起越来越多的关注。然而，抗生素的过度使用以及形成生物膜的特性使得治疗具有挑战性。在本研究中，研究了一种来源于plectasin的肽NZ2114对其体内和体外的抗菌活性及作用机制。NZ2114对其表现出强大的抗菌活性（最低抑菌浓度，MIC = 0.23 μM），诱导耐药突变的可能性较低且具有高效杀菌作用，优于莫匹罗星（MIC = 0.25 - 0.5 μM）和林可霉素（MIC = 4.34 - 69.41 μM）。电子显微镜和流式细胞术结果表明，NZ2114破坏了细胞膜，导致细胞内容物泄漏、细胞质膜收缩，最终细胞死亡。细胞内ROS活性和Alamar Blue检测表明，NZ2114干扰细胞内代谢过程。此外，NZ2114有效抑制生物膜形成，共聚焦激光扫描显微镜进一步揭示了其抗菌和抗生物膜活性（生物膜厚度降至6.90 - 17.70μm）。NZ2114在小鼠脓疱病模型中的体内治疗表明，它在有效减少皮肤细菌数量、减轻组织学损伤和减少皮肤损伤面积方面优于林可霉素。这些结果表明，NZ2114可能是一种有前途的抗感染抗菌候选药物。
