Potential of Antimicrobial Peptide Synergies for Combating Infectious Diseases in Aquaculture: A Review

The increasing emergence of antimicrobial resistance in aquaculture has highlighted the urgent need for alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) are promising candidates because of their broad-spectrum antimicrobial activity, multitarget mechanisms, and low propensity to induce resistance. However, their application is limited by poor stability, rapid degradation, and low bioavailability. This review summarizes recent advances in AMP-based synergistic strategies for controlling infectious diseases in aquaculture, including AMP-antibiotic, AMP-polysaccharide, AMP-herbal extract, and AMP-AMP combinations. Current evidence indicates that these strategies can enhance antimicrobial efficacy, reduce effective dosages, delay resistance development, improve AMP stability and delivery, and strengthen host immune responses. The underlying mechanisms involve membrane permeabilization, biofilm disruption, metabolic interference, controlled release, targeted delivery, and immunomodulation. Among these approaches, AMP-antibiotic combinations improve the effectiveness of existing antibiotics, while polysaccharide-based systems enhance peptide stability and bioavailability. AMP-herbal extract and AMP-AMP combinations further broaden antimicrobial activity through complementary mechanisms. Overall, AMP-based synergistic strategies represent promising alternatives for reducing antibiotic dependence in aquaculture. Future studies should focus on mechanistic validation, delivery optimization, field-scale evaluation, and regulatory development to facilitate their practical application.