High manufacturing costs and weak cell selectivity have limited the clinical application of naturally occurring peptides when faced with an outbreak of drug resistance. To overcome these limitations, a set of antimicrobial peptides was synthesized with the general sequence of (WL)n, where n = 1, 2, 3, and WL was truncated from the N‐terminus of Cecropin P1 without initial serine residues. The antimicrobial peptide WL3 exhibited stronger antimicrobial activity against both Gram‐negative and Gram‐positive microbes than the parental peptide CP‐1. WL3 showed no hemolysis even at the highest test concentrations compared to the parental peptide CP‐1. The condition sensitivity assays (salts, serum, and trypsin) demonstrated that WL3 had high stability in vitro. Fluorescence spectroscopy and electron microscopy indicated that WL3 killed microbes by means of penetrating the membrane and causing cell lysis. In a mouse model, WL3 was able to significantly reduce the bacteria load in major organs and cytokines (TNF‐α, IL‐6, and IL‐1β) levels in serum. In summary, these findings suggest that WL3, which was modified from a natural antimicrobial peptide, has enormous potential for application as a novel antibacterial agent.

中文翻译：

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猪线虫抗菌肽CP-1氨基末端片段的抗菌活性和分子机制

当面对耐药性爆发时，高制造成本和较弱的细胞选择性限制了天然多肽的临床应用。为了克服这些限制，合成了一组抗菌肽，其一般序列为（WL）n，其中n = 1、2、3和WL从天蚕素P1的N末端被截短，没有最初的丝氨酸残基。抗菌肽WL3对革兰氏阴性菌和革兰氏阳性菌均比亲本肽CP-1表现出更强的抗菌活性。与亲本肽CP-1相比，即使在最高测试浓度下，WL3也无溶血现象。条件敏感性试验（盐，血清和胰蛋白酶）表明WL3在体外具有很高的稳定性。荧光光谱和电子显微镜表明，WL3通过穿透膜杀死细菌，并引起细胞裂解。在小鼠模型中，WL3能够显着降低血清中主要器官的细菌负荷和细胞因子（TNF-α，IL-6和IL-1β）水平。总而言之，这些发现表明WL3，