Aeromonas hydrophila, a gram-negative pathogen prevalent in aquatic environments, is a known inducer of septicemia in aquatic animals, causing considerable losses in aquaculture. The limited effectiveness of conventional drug therapies underscores the need for exploring innovative treatment strategies. Gene knockout technology presents a promising approach for exploring the immune response in zebrafish and developing therapeutic interventions for aquatic organisms diseases. This study focuses on elucidating the mechanism of action of phd3 in zebrafish against Aeromonas hydrophila through the creation of a phd3 knockout model. Our findings reveal a high degree of conservation of phd3 sequences between zebrafish and commercially important fish species, making it a suitable model organism for studying fish inflammation. Knocking out phd3 significantly improved the resistance of zebrafish to Aeromonas hydrophila, reduced tissue damage, increased survival rates, and decreased bacterial burden. Furthermore, the downregulation of phd3 enhanced immune responses, antioxidant levels, endoplasmic reticulum stress, autophagy reactions and apoptosis. This research underscores the crucial role of phd3 in zebrafish innate immunity, offering novel insights into the prevention and management of diseases in aquatic organisms, and potential immunotherapeutic strategies. Our findings have significant implications for the future development of targeted therapeutic strategies against Aeromonas hydrophila and other aquatic pathogens.
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