Anti-Pseudomonas aeruginosa Activity of the Scorpion-Derived Peptide GK8

The increasing infection and antibiotic resistance of Pseudomonas aeruginosa has become a major threat to public health, making exploring new and effective antimicrobial agents particularly important. In this study, the scorpion-derived cationic peptide GK8 was designed, which showed effectiveness against P. aeruginosa including clinical resistance strains with low hemolytic activity. In the mouse skin subcutaneous infection model, GK8 significantly decreased the number of P. aeruginosa cells and inflammatory infiltration in the infected area. Mechanism research showed that GK8 killed P. aeruginosa in a concentration- and time-dependent manner, damaging the membrane integrity and membrane potential, inducing ROS accumulation, and interacting with nucleic acids. Moreover, GK8 could inhibit the pathogenic factors of P. aeruginosa, including inhibiting adhesion, motility, pyocyanin production, protease and elastase activities, and biofilm formation. Taken together, GK8 could be a potential alternative anti-infective agent against skin infection caused by P. aeruginosa.