基于片段融合策略发现抗耐药菌的新型抗菌肽。
The discovery of novel antimicrobial peptides against drug-resistant bacteria based on fragments fusion strategy.
作者信息
Zeng Chunlan, Ning Ziyao, Xu Yijie, Tian Long, Jing Jie, Chen Longming, Ye Weifeng, Han Jiaqi, Wang Taoran, Meng Zhao, Meng Qingbin
机构信息
State Key Laboratory of National Security Specially Needed Medicines, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Center of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
出版信息
Eur J Med Chem. 2025 May 5;289:117493. doi: 10.1016/j.ejmech.2025.117493. Epub 2025 Mar 8.
Since the escalating prevalence of multidrug-resistant (MDR) bacterial infections posing global health challenges, novel antimicrobial agents are urgently needed. This study designed a series of antimicrobial peptides by fusing two fragments of antimicrobial peptides sC18 (1-9) and MSI-78 (10-16). Among these peptides, 13DKDab exhibited broad-spectrum antimicrobial efficacy against six different MDR bacterial strains with relatively low MICs. It exerted antibacterial effects through a membrane-disruption mechanism and maintained high stability in serum environment. Moreover, 13DKDab displayed low cytotoxicity and hemolysis in vitro, and significant therapeutic efficacy in a mouse acute peritonitis model. These findings demonstrate that 13DKDab is a promising antimicrobial agent in counteracting multidrug-resistant bacterial infections.
由于多重耐药（MDR）细菌感染的患病率不断上升，给全球健康带来挑战，因此迫切需要新型抗菌剂。本研究通过融合抗菌肽sC18（1-9）和MSI-78（10-16）的两个片段设计了一系列抗菌肽。在这些肽中，13DKDab对六种不同的多重耐药菌株表现出广谱抗菌活性，且最低抑菌浓度（MIC）相对较低。它通过膜破坏机制发挥抗菌作用，并在血清环境中保持高稳定性。此外，13DKDab在体外表现出低细胞毒性和溶血作用，并在小鼠急性腹膜炎模型中具有显著的治疗效果。这些发现表明，13DKDab是一种有前途的抗多重耐药细菌感染的抗菌剂。
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