Immunometabolic interplay and molecular characterization of hepcidins reveal ferroptosis mechanisms to Edwardsiella piscicida infection in black rockfish Sebastes schlegeli.

Edwardsiella piscicida infection represents a major pathogenic threat in aquaculture, yet the molecular mechanisms underlying host-pathogen interactions is still not fully understood. Here, we investigated the pathophysiological response of black rockfish Sebastes schlegeli to E. piscicida infection through an integrated approach combining immune-metabolism analysis and molecular characterization. Infected fish displayed severe pathological manifestations, including melanin deposition, visceral swelling, and extensive hepatic damage, with mortality reaching 80 % by day 15 post-infection. Transcriptomic analysis identified 5363 differentially expressed genes, while metabolomic profiling revealed 194 altered metabolites. Integration of these datasets demonstrated significant perturbations in key metabolic pathways, including glutathione metabolism, nucleotide metabolism, and energy metabolism, highlighting the host's metabolic reprogramming in response to infection. Notably, we identified ferroptosis as a key mechanism of E. piscicida-induced tissue damage, characterized by glutathione depletion and dysregulation of iron homeostasis genes. Furthermore, we characterized two hepcidin genes (Sshepcidin 1 and Sshepcidin 2) that exhibited tissue-specific expression patterns and were significantly upregulated following bacterial challenge. Synthetic mature peptides demonstrated broad-spectrum antibacterial activity against various bacterial pathogens, with mSshep 1 exhibiting greater overall potency than mSshep 2. These findings provide novel insights into the molecular underpinnings of black rockfish response to E. piscicida infection and highlight potential targets for therapeutic intervention in aquaculture systems.