The evolution of Staphylococcus aureus (S. aureus) with the ability to acquire and develop resistance to antibiotics has been described as a distinct strain emergence event. Methicillin-resistant S. aureus (MRSA) is responsible for most global S. aureus bacteremia cases. Bacterial biofilms are one of the primary reasons for drug resistance. Biofilms formed by S. aureus are the most common cause of biofilm-associated infections, which increase the difficulty of treatment. Antimicrobial peptides (AMPs) represent promising candidates for the future treatment of antibiotic-resistant bacterial and biofilm-associated infections. In this study, we designed and synthesized a series of analogs to increase the druggability of the natural antimicrobial peptide CPF-C1. Among the analogs, CPF-2 showed high antimicrobial activity against MRSA and multidrug-resistant S. aureus isolated from clinics. In the serum and physiological salt environment, CPF-2 also exhibited effective antimicrobial activity. Importantly, CPF-2 did not determine resistance and showed no hemolytic activity at the active concentration. Concerning the mechanism of action, CPF-2 produced a rapid bactericidal effect by interrupting the bacterial membranes. Even more surprisingly, CPF-2 showed an excellent ability to prevent and eradicate biofilms caused by S. aureus and MRSA not only in vitro but also in vivo. Our results suggested that CPF-2 has potential as a lead compound to treat infections caused by S. aureus and MRSA, including the associated biofilms.

具有获得和发展对抗生素抗性的能力的金黄色葡萄球菌（金黄色葡萄球菌）的进化已被描述为独特的菌株出现事件。耐甲氧西林金黄色葡萄球菌（MRSA）负责大多数全球金黄色葡萄球菌菌血症病例。细菌生物膜是产生耐药性的主要原因之一。金黄色葡萄球菌形成的生物膜是生物膜相关感染的最常见原因，这增加了治疗的难度。抗菌肽（AMPs）代表了有前途的候选药物，可用于未来治疗耐药性细菌和生物膜相关感染。在这项研究中，我们设计并合成了一系列类似物，以增加天然抗菌肽CPF-C1的可药用性。在类似物中，CPF-2对MRSA和耐多药金黄色葡萄球菌显示出很高的抗菌活性。与诊所隔离。在血清和生理盐环境中，CPF-2也表现出有效的抗菌活性。重要的是，CPF-2不能确定耐药性，在有效浓度下也没有溶血活性。关于作用机理，CPF-2通过打断细菌膜产生快速的杀菌作用。更令人惊讶的是，CPF-2不仅在体外而且在体内都显示出优异的预防和根除金黄色葡萄球菌和MRSA引起的生物膜的能力。我们的结果表明，CPF-2有潜力作为治疗金黄色葡萄球菌和MRSA（包括相关生物膜）引起的感染的先导化合物。