Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae are a serious worldwide public health concern due to the ineffectiveness of empirical antibiotic therapy. Therefore, research and the development of new antibiotic alternatives are urgently needed to control these bacteria. The use of cationic antimicrobial peptides (CAMPs) is a promising candidate alternative therapeutic strategy to antibiotics because they exhibit antibacterial activity against both antibiotic susceptible and MDR strains. In this study, we aimed to investigate the in vitro antibacterial effect of a short synthetic CAMP derived from the ΔM2 analog of Cec D-like (CAMP-CecD) against clinical isolates of K pneumoniae (n = 30) and P aeruginosa (n = 30), as well as its hemolytic activity. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of CAMP-CecD against wild-type and MDR strains were determined by the broth microdilution test. In addition, an in silico molecular dynamic simulation was performed to predict the interaction between CAMP-CecD and membrane models of K pneumoniae and P aeruginosa. The results revealed a bactericidal effect of CAMP-CecD against both wild-type and resistant strains, but MDR P aeruginosa showed higher susceptibility to this peptide with MIC values between 32 and >256 μg/mL. CAMP-CecD showed higher stability in the P aeruginosa membrane model compared with the K pneumoniae model due to the greater number of noncovalent interactions with phospholipid 1-Palmitoyl-2-oleyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG). This may be related to the boosted effectiveness of the peptide against P aeruginosa clinical isolates. Given the antibacterial activity of CAMP-CecD against wild-type and MDR clinical isolates of P aeruginosa and K pneumoniae and its nonhemolytic effects on human erythrocytes, CAMP-CecD may be a promising alternative to conventional antibiotics.

由于经验性抗生素治疗无效，由多重耐药性（MDR）的铜绿假单胞菌和肺炎克雷伯菌引起的感染引起了全世界的严重公共卫生关注。因此，迫切需要研究和开发新的抗生素替代品来控制这些细菌。阳离子抗菌肽（CAMP）的使用是一种有希望的替代抗生素治疗方法，因为它们对抗生素敏感和MDR菌株均表现出抗菌活性。在这项研究中，我们旨在研究源自Cec D-like的ΔM2类似物（CAMP-CecD）的短合成CAMP对肺炎克雷伯氏菌（n = 30）和临床分离株的体外抗菌作用。铜绿假单胞菌（n = 30）及其溶血活性。通过肉汤微量稀释试验确定了CAMP-CecD对野生型和MDR菌株的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）。此外，进行了计算机分子动力学模拟，以预测CAMP-CecD与肺炎克雷伯菌和铜绿假单胞菌的膜模型之间的相互作用。结果表明，CAMP-CecD对野生型和耐药菌株均具有杀菌作用，但铜绿多药耐药性对这种肽的敏感性更高，MIC值为32至> 256μg/ mL。与铜绿假单胞菌膜模型相比，CAMP-CecD在铜绿假单胞菌膜模型中显示出更高的稳定性。肺炎克雷伯菌模型是由于与磷脂1-Palmitoyl-2-oleyl-sn-glycero-3-（phospho-rac-（1-glycerol））（POPG）的非共价相互作用数量增加。这可能与该肽对铜绿假单胞菌临床分离株的增强效力有关。鉴于CAMP-CecD对铜绿假单胞菌和肺炎克雷伯菌的野生型和MDR临床分离株的抗菌活性及其对人红细胞的非溶血作用，CAMP-CecD可能是常规抗生素的有前途的替代品。