Abstract

Background/Objectives: The frequent use of antibiotics has led to increasing drug resistance inAeromonas hydrophila; therefore, there is an urgent need to develop novel antimicrobial agents to prevent and control bacterial diseases in aquaculture. Allicin E (ALE) is derived from garlic (Allium sativumL.), a plant extensively used in traditional medicine for treating infections. This study aimed to evaluate the potential of ALE againstA. hydrophila, a major aquaculture pathogen, by investigating its antibacterial efficacy, mechanisms of action, and in vivo protective effects.Methods: The minimum inhibitory and bactericidal concentrations (MIC/MBC) were determined by broth microdilution. Antibacterial mechanisms were investigated through ROS detection, electron microscopy, fluorescent staining, and content leakage measurement. In vivo efficacy was evaluated inCarassius auratus gibelioby monitoring survival rates and bacterial loads, analyzing immune and antioxidant biomarkers, and histopathological analysis afterA. hydrophilachallenge.Results: ALE exhibited potent antibacterial activity (MIC = MBC = 8 μg/mL), achieving complete bacterial elimination within 1 h and showing a low resistance propensity. Mechanistically, ALE induced ROS accumulation, causing oxidative damage that disrupted membrane integrity and facilitated the leakage of cellular contents. In vivo, ALE significantly enhanced fish survival, reduced bacterial loads, modulated inflammatory cytokines, boosted antioxidant enzyme activities (SOD and CAT), and alleviated tissue damage.Conclusions: ALE possesses potent in vitro antibacterial activity and exerts an inhibitory effect on bacteria-induced inflammatory responses, effectively combatingA. hydrophilathrough a multi-target mechanism and enhancing host resistance.