We developed two short helical antimicrobial peptides, HVF18-a3 and its d-enantiomer, HVF18-a3-d, derived from the thrombin C-terminal peptide HVF18. These peptides exhibit potent antimicrobial activity against various bacteria by compromising both the outer and inner membranes, with low hemolytic activity. They are stable in the presence of physiological salts and human serum, exhibiting a low potential for developing drug resistance and excellent antibiofilm activity against Gram-negative bacteria. HVF18-a3-d also neutralized lipopolysaccharide (LPS) through direct binding interactions and suppressed the production of inflammatory cytokines through the inflammatory signaling pathway mediated by Toll-like receptor 4 in RAW264.7 cells stimulated with LPS. Both pre- and post-treatment with HVF18-a3-d significantly protected mice against fatal septic shock induced by carbapenem resistant Acinetobacter baumannii. These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates for developing antibiotics against Gram-negative sepsis.

中文翻译：

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脓毒症模型中新型凝血酶衍生肽的抗菌、抗生物膜和抗炎作用：深入了解潜在机制


我们开发了两种短螺旋抗菌肽 HVF18-a3 及其 d 对映异构体 HVF18-a3-d，源自凝血酶 C 端肽 HVF18。这些肽通过破坏外膜和内膜，表现出对各种细菌的强效抗菌活性，溶血活性低。它们在生理盐和人血清存在下稳定，表现出产生耐药性的低潜力和对革兰氏阴性菌的出色抗生物膜活性。HVF18-a3-d 还通过直接结合相互作用中和脂多糖 （LPS），并通过 LPS 刺激的 RAW264.7 细胞中由 Toll 样受体 4 介导的炎症信号通路抑制炎性细胞因子的产生。用 HVF18-a3-d 处理前后均显着保护小鼠免受碳青霉烯类耐药鲍曼不动杆菌诱导的致命感染性休克。这些发现表明 HVF18-a3 和 HVF18-a3-d 是开发针对革兰氏阴性脓毒症的抗生素的有希望的候选者。