The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC₅₀ = 55.31 ± 5.00 µM) and its hemolytic activity (HC₅₀ = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

抗生素耐药细菌，特别是碳青霉烯类耐药鲍曼不动杆菌（CRAB）的出现，加上有效抗生素开发的相对停滞，导致了巨大的健康和经济问题。在这项研究中，我们旨在描述 LyeTx I mnΔK（一种基于红颌狼蛛毒液 LyeTx I 的短合成肽）针对 CRAB 的抗菌谱。 LyeTx I mnΔK 对广泛耐药的鲍曼不动杆菌表现出相当大的抗菌活性，最低抑制浓度和杀菌浓度分别为 1 至 16 µM 和 2 至 32 µM。该肽显着增加了 CRAB 中 260 nm 吸收细胞内物质的释放，表明存在溶菌作用。 LyeTx I mnΔK 与美罗培南和粘菌素对 CRAB 具有协同作用。 LyeTx I mnΔK 对 Vero 细胞的细胞毒性浓度 (CC ₅₀ = 55.31 ± 5.00 µM) 及其溶血活性 (HC ₅₀ = 77.07 ± 4.00 µM) 相当低；然而，在人类和动物血清和胰蛋白酶存在下，其抗菌活性显着降低。然而，吸入这种肽可以有效减少 CRAB 感染小鼠模型的肺部细菌负荷。总而言之，这些结果表明肽 LyeTx I mnΔK 是开发针对 CRAB 的新型有效且安全的抗菌剂的潜在原型。