Natural Antibacterial Compounds from Aquatic Animals for Controlling Fish Pathogenic Bacteria: Mechanisms, Efficacy, and Prospects for Sustainable Aquaculture

Aquaculture faces escalating bacterial disease burdens and mounting antimicrobial resistance (AMR) driven by intensive production and extensive antibiotic use, threatening animal health, productivity, and One Health security. This review synthesizes current knowledge on natural antibacterial compounds derived from aquatic animals, with a primary focus on antimicrobial peptides (AMPs) and related metabolites from finfish, crustaceans, mollusks, echinoderms, gastropods, cnidarians, and other invertebrates. After outlining the global status of major Gram-negative and Gram-positive fish and shellfish pathogens, their infection routes, and the limitations of conventional control measures, the review critically examines skin mucus, serum and organ factors, hemolymph-derived AMPs, tissue lectins, and non protein bioactives such as chitin, chitosan, and carotenoids. Particular emphasis is placed on cationic, α helical AMPs (≈350 reported from aquatic invertebrates) that exhibit broad-spectrum activity against Vibrio spp., Aeromonas spp., Streptococcus spp., Staphylococcus aureus, Escherichia coli, and Salmonella through membrane disruption, intracellular targeting, and immunomodulation, often with lower resistance propensity than conventional antibiotics. Less conventional sources, including echinoderms, gastropods, and cnidarians, are highlighted for their structurally diverse peptides, saponins, and microbiome-derived metabolites that show promising in vitro and in vivo efficacy and compatibility with saline environments. The review further discusses omics driven discovery, bioinformatics-guided peptide design, and biotechnological production (recombinant systems, synthetic analogs, and valorization of processing by products) as key enablers for scale up and standardization. Finally, major challenges—variability of natural sources, cost, regulatory hurdles, safety, and environmental fate—are evaluated alongside research and policy priorities needed to translate aquatic-animal-derived antibacterials into integrated, commercially viable tools for sustainable, antibiotic sparing aquaculture.