A novel antimicrobial peptide Scyreptin from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.

Antimicrobial resistance (AMR) constitutes a significant global threat to human health. In recent years, there has been a concerning surge in infections caused by multidrug-resistant bacteria, highlighting the pressing need to urgently explore novel and effective alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as a focal point of research, capturing significant attention as promising antimicrobial agents. In this study, we have identified a novel cationic antimicrobial peptide (AMP) named Scyreptin, derived from the marine invertebrate Scylla paramamosain. The results showed that Scyreptin exhibits a broad-spectrum antimicrobial activity, demonstrating significant potency against both bacteria and fungi, and even against the clinically isolated multidrug-resistant bacteria Pseudomonas aeruginosa. Moreover, Scyreptin exhibited rapid bactericidal kinetic. The results of antibacterial mechanism showed that Scyreptin destroyed the integrity of bacterial membranes, leading to bacterial death and exhibited potent anti-biofilm activity against P. aeruginosa. The activity of Scyreptin against bacteria had a favorable thermal stability, displayed a certain ion tolerance, and showed no discernible cytotoxicity when assessed against both the mammalian cell line HEK293T and the fish cell lines ZF4. In an In vivo study, Scyreptin exhibited a remarkably reduction in the bacterial load caused by multidrug-resistant P. aeruginosa at the site of infection, and promoted wound healing in a mouse model of burn infection. This study indicated that Scyreptin holds promise as an effective antibacterial agent, potentially serving as a topical skin treatment against multidrug-resistant bacterial infections, including those caused by P. aeruginosa.