Studies on Phenylalanine Metabolism in Enhancing the ε-Polylysine-Mediated Killing Effect of Oxytetracycline-resistant Aeromonas hydrophila

Notably, supplementation with downregulated exogenous metabolites significantly enhanced the bactericidal effect of ε-PL, with 2-phenylacetamide exhibiting the strongest synergistic effect (up to 436-fold), at which point intracellular ε-PL concentration reached 50.26 μg/mg protein. Conclusion: These results demonstrated the phenylalanine metabolic pathway is the key pathway through which ε-PL exerts its bactericidal effect against OTC-A01.

This study innovatively applied non-targeted metabolomics to identify this pathway as a critical metabolic target, and was the first to demonstrate that exogenous metabolite supplementation enhances ε-PL efficiency via metabolic reprogramming. This work uncovered a novel molecular mechanism of ε-PL’s antibacterial activity and provides theoretical support for developing antimicrobial strategies targeting bacterial metabolism, with significance for addressing A. hydrophila antibiotic resistance in aquaculture and public health.