Phage-displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus.

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.