PA2(SQRKLAAKLTSK) is a targeting peptide that binds specifically to OprF porin on P. aeruginosa was identified by phage display peptide library screening. GNU7(RLLRPLLQLLKQKLR) is a de novo generated short a-helical AMP, displayed broad-spectrum activities against bacteria and fungi, including against clinically isolated drug-resistant strains under physiological salt and serum conditions, without cytotoxicity to human cells. Hybrid peptide PA2-GNU7 exhibited potent antimicrobial activity against P. aeruginosa without causing host toxicity. Confocal laser scanning microscopy analysis and time-kill experiments demonstrated that PA2-GNU7 exhibited a high degree of specificity for P. aeruginosa, and rapidly and selectively killed P. aeruginosa cells in mixed cultures. In addition, in vivo treatment efficacy of PA2-GNU7 was significantly greater than that of conventional antibiotics in a mouse model of MDR P. aeruginosa infection. PA2-GNU7 may be a promising template for further development as a novel anti-MDR P. aeruginosa therapeutic agent.
Kim H, Jang JH, Kim SC, Cho JH. Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa. Eur J Med Chem. 2020