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

• Published in: Fish & shellfish immunology Vol. 165; p. 110505
• Main Authors: Nong, Yanhong, Liu, Qionglin, Xu, Jing, Wei, Gonghong, Liao, Yining, Zhou, Yuanyuan, Chen, Xinhua, Zhang, Xiang-Yang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2025
• Subjects: Amino Acid Sequence; amino acid substitution; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial properties; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; aquaculture industry; bacteria; cell membranes; CXCL8; cytotoxicity; Danio rerio; Fish Diseases - immunology; Fish Diseases - microbiology; Fish Proteins - chemistry; Fish Proteins - genetics; Fish Proteins - immunology; Fish Proteins - pharmacology; hemolysis; IL-8; immunology; Interleukin-8 - chemistry; Interleukin-8 - genetics; Interleukin-8 - immunology; Large yellow croaker (Larmichthys crocea); Larimichthys crocea; lipopolysaccharides; membrane permeability; Perciformes - immunology; protective effect; Protein Conformation, alpha-Helical; shellfish; survival rate; therapeutics; Visceral white nodule disease; Zebrafish; CXCL8; IL-8; Visceral white nodule disease; Large yellow croaker (Larmichthys crocea); Antimicrobial peptides
• ISSN: 1050-4648; 1095-9947; 1095-9947
• DOI: 10.1016/j.fsi.2025.110505

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. •Two 13-amino acid peptides, AVV13N (derived from large yellow croaker CXCL8) and its enhanced variant AVK13N, were designed as potential antibiotic alternatives.•Both peptides exhibit broad-spectrum antimicrobial effects, with AVK13N showing significantly higher efficacy than AVV13N.•The peptides demonstrate low cytotoxicity, minimal hemolysis, and retain activity under varying temperatures, pH levels, and most physiological salts.•They kill bacteria by depolarizing membranes, increasing permeability via LPS binding, and disrupting cell structure.•Treatment with these peptides improves survival in zebrafish infected with P. plecoglossicida, highlighting their therapeutic potential in aquaculture.