Vitamin Dpretreatment outperforms post-infection supplementation in suppressing ferroptosis and enhancing bacterial clearance during Edwardsiella tarda infection in hybrid yellow catfish (Pelteobagrus fulvidraco♀ ×Pelteobagrus vachelli♂).

Abstract

Edwardsiella tarda (E. tarda) is a facultative intracellular pathogen that causes systemic infections in fish and threatens intensive aquaculture. It disrupts iron homeostasis and induces oxidative stress, thereby potentially triggering ferroptosis. Although Vitamin D(VD) has been reported to mitigate E. tarda infection, the time-dependent mechanisms linked to ferroptosis remain unclear. To address this gap, hybrid yellow catfish (Pelteobagrus fulvidraco♀ × Pelteobagrus vachelli♂) were allocated to four groups: control, infection, VDpretreatment (VE), and post-infection supplementation (EV). We performed an integrated assessment using metabolomics and transcriptomics, biochemical assays, histology, and Transmission Electron Microscopy (TEM). E. tarda infection induced oxidative stress and inflammatory responses, while simultaneously evading host immune defense mechanisms. From the perspective of ferroptosis, the infection disrupted iron metabolism and promoted the occurrence of ferroptosis. VDpretreatment regulated iron and redox balance through glutathione (GSH), suppressed ferroptosis, maintained membrane lipid homeostasis, and facilitated pathogen clearance and tissue repair. In contrast, EV modulated inflammatory responses and mitigated ferroptosis-related damage by regulating iron metabolism and downregulating ACSL4, though its overall protective effect was weaker than that of pretreatment. Overall, VDalleviated E. tarda-induced ferroptosis, oxidative stress, and metabolic disruption in a time-dependent manner, with early intervention showing stronger protection in limiting ferroptosis, enhancing immunity, and repairing tissue damage.