Chlorine dioxide suppresses Aeromonas through thiol oxidation and modulates hepatic redox-immune responses in Aeromonas salmonicida-infected rainbow trout (Oncorhynchus mykiss).

Chlorine dioxide (ClO2) is a potent oxidative disinfectant with potential use in bacterial disease control; however, its antibacterial mechanism and its influence on host redox-immune responses during Aeromonas salmonicida infection in rainbow trout (Oncorhynchus mykiss) remain unclear. Here, we evaluated the antibacterial activity of ClO2 against common bacterial pathogens, examined its thiol-targeting antibacterial mechanism, and characterized host toxicity, innate immune responses, oxidative stress, and hepatic transcriptomic regulation. ClO2 markedly inhibited Aeromonas hydrophila and A. salmonicida and reduced bacterial thiol contents in a concentration-dependent manner, indicating that thiol-associated oxidative damage contributes to its antibacterial action. Acute exposure revealed dose-dependent host responses: low-to-moderate ClO2 exposure activated antioxidant and innate immune responses, whereas higher concentrations caused mortality, liver and gill injury, glutathione depletion, lipid peroxidation, and immune disturbance. RNA-seq analysis showed that ClO2 exposure and A. salmonicida infection both affected xenobiotic metabolism, glutathione metabolism, lipid metabolism, and immune-related pathways. In the AsClO2 vs As comparison, 1,877 differentially expressed genes were identified and were mainly enriched in drug metabolism-cytochrome P450, cytochrome P450-mediated xenobiotic metabolism, glutathione metabolism, PPAR signaling, C-type lectin receptor signaling, and cytokine-cytokine receptor interactions. qRT-PCR confirmed the regulation of representative immune-metabolic genes, including mmp9, fmo5, cyp3a27, mgst1, fabp1, apoa-i-2, and bnip3. These findings indicate that ClO2 suppresses Aeromonas through thiol-associated oxidative damage while modulating hepatic redox-immune and metabolic networks during bacterial infection, providing new insight into host-pathogen-disinfectant interactions in rainbow trout.