Antimicrobial activity and synergistic effect of phage-encoded antimicrobial peptides with colistin and outer membrane permeabilizing agents against <i>Acinetobacter baumannii</i>

Peptides PE04-1, PE04-1(NH₂), and PE04-2 showed sequence similarity to mammalian cathelicidin antimicrobial peptides. They are cationic peptides with a positive charge, exhibiting high hydrophobic ratios and high hydropathy values. The modified PE04-2 was designed by enhancing cationic through amino acid substitutions and shows powerful antibiofilm effects due to its cationic, amphipathic, and hydrophobic properties to destroy biofilm. The peptides improved survival rates in <i>G. mellonella</i> infection models and showed no cytotoxicity effect on human cell lines, ensuring their safety for potential therapeutic applications. In conclusion, this study highlights the antimicrobial ability of phage-encoded peptides against multidrug-resistant <i>A. baumannii</i>. It can be an innovative tool, paving the way for future research to optimize their clinical application.