Pecbloodin: a promising antimicrobial peptide fromwith therapeutic potential againstinfection.

Abstract

is a significant pathogen in aquaculture, causing severe systemic infections and considerable economic losses worldwide. The limited efficacy of current treatments and the emergence of multidrug-resistant strains underscore the urgent need for novel antimicrobial strategies. Antimicrobial peptides have garnered increasing interest due to their broad-spectrum activity and low risk of resistance development. In this study, we identified a novel immune-related gene from the mudskipper, named, which encodes a mature peptide of 67 amino acids. A truncated peptide derived from this sequence, Pecbloodin, exhibited broad-spectrum antibacterial activity, high thermal stability, and tolerance to sodium ions. Functional assays demonstrated that Pecbloodinexerts rapid bactericidal effects by compromising bacterial membrane integrity, inducing cellular content leakage, and triggering endogenous reactive oxygen species accumulation. Furthermore, it effectively inhibited bacterial biofilm formation and did not promote resistance under prolonged exposure. Importantly,experiments using an-infected mudskipper model revealed that Pecbloodinsignificantly improved host survival and modulated the immune response. Overall, Pecbloodinshows great potential as a promising alternative to conventional antibiotics for the control ofinfections in aquaculture, addressing the pressing issue of antibiotic resistance.IMPORTANCEis an urgent threat to global aquaculture. We mined the mudskippergenome for antimicrobial peptide and identified Pecbloodin, a 20-aa thermostable peptide that rapidly permeabilizes bacterial membranes, elicits intracellular reactive oxygen species, blocks biofilm formation, and does not select for resistance. In-challenged fish, a single dose reduced mortality by 25% and restored immune homeostasis. The peptide is readily synthesized and feed-compatible, providing an immediate, resistance-proof substitute for conventional antibiotics in fish farming.