Peptides derived from the α-helical structure of large yellow croaker (Larimichthys crocea) CXCL8 demonstrate potent bactericidal effects.

Bacterial diseases pose a significant threat to the large yellow croaker aquaculture industry, and the overuse of antibiotics has exacerbated the issue of bacterial resistance. Consequently, there is an urgent need for antimicrobial peptides as alternatives to traditional antibiotics. In this study, a 13-amino acid peptide, AVV13N, was designed by truncating the carboxyl-terminal region of the large yellow croaker CXCL8 protein and amidating its carboxyl terminus. A derivative peptide, AVK13N, was subsequently synthesized through amino acid substitution. In vitro assays demonstrated that both peptides exhibit broad-spectrum antimicrobial activity, with AVK13N showing significantly stronger efficacy than AVV13N. Cytotoxicity and hemolytic activity tests confirmed that these two peptides have low cytotoxicity and minimal hemolytic effects. Stability analysis further revealed that two peptides maintain their bactericidal activity under varying temperatures and pH levels, and in the presence of most physiological salts. Mechanistically, the two peptides depolarize the bacterial cytoplasmic membrane and enhance membrane permeability by binding to lipopolysaccharide (LPS), ultimately disrupting bacterial cell structure, thus exerting bactericidal effects. In vivo experiments demonstrated that both peptides improve the survival rate of zebrafish (Danio rerio) infected with P. plecoglossicida, with AVK13N exhibiting a particularly pronounced protective effect. These findings not only elucidate the direct bactericidal activity of the carboxyl-terminal α-helical peptides derived from large yellow croaker CXCL8, but also underscore their potential as therapeutic agents for the prevention and control of bacterial diseases in fish.