PDF(Pubmed)
Abstract：
Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.
摘要：
广谱抗菌药物往往缺乏特异性,导致不分青红皂白的杀菌活动，这可能会破坏宿主菌群的正常微生物平衡，并在全身给药过程中引起不必要的细胞毒性。在这项研究中,我们通过将噬菌体展示肽引入广谱抗菌肽上,构建了针对金黄色葡萄球菌的特异性靶向抗菌肽,并通过单因素修饰探索了其结构-功能关系.通过基于选择性指数和靶向指数的筛选获得的SFK2显示出对金黄色葡萄球菌的特异性杀伤能力。此外，SFK2在小鼠和仔猪中显示出优异的生物相容性，并证明了对金黄色葡萄球菌感染的显着治疗效果。总之,我们筛选的噬菌体衍生七肽有效地增强了抗菌肽对金黄色葡萄球菌的特异性杀菌能力，为开发靶向抗菌肽提供理论依据。
