Pseudomonas plecoglossicida hijacks host glycolysis to induce hypoglycemic shock in large yellow croakers (Larimichthys crocea)

Bacterial sepsis frequently progresses to hypoglycemia, a metabolic condition strongly associated with increased mortality. In this study, large yellow croakers were injected with phosphate-buffered saline (PBS) to establish a control group (CG) or exposed to an equivalent dose of Pseudomonas plecoglossicida, after which infected fish were categorized into moribund group (MG) or survival group (SG). Results showed that hepatic glycogen was rapidly depleted across all infected croakers, but severe hypoglycemia emerged only in the MG group, with blood glucose reduced to 0.80 mmol/L. Infection produced substantial oxidative and redox disruption, including accumulation of lipid peroxides, depletion of reduced glutathione (GSH), and a decline in the NAD⁺/NADH ratio, although these fluctuations were markedly attenuated in the SG group compared to the MG group. MG group exhibited widespread metabolic deterioration, characterized by reduced intermediates across glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation, decreased glycerides and fatty acids, clear mitochondrial swelling with cristae loss, and strong suppression of G6pc transcription. SG group displayed a distinct metabolic reconfiguration involving altered abundance of 26 lipid species (18 increased and eight decreased) and 13 carbohydrates (nine increased and four decreased). The most pronounced fluctuations were observed in the glycogen-shunt products, maltose elevated 47.78-fold relative to the CG and 7 995-fold relative to the MG, and D-(+)-trehalose elevated by 964.08-fold and 1 106.38-fold, respectively. Functional analyses identified pptse6 (ACRRS2_13720), a type VI secretion system (T6SS) effector, as a key virulence gene in P. plecoglossicida, whose absence reduced bacterial virulence by 808-fold. Another competitive T6SS effector, TreS, contributed to maltose and D-(+)-trehalose synthesis, with its deletion lowering production of these metabolites by 7.75-fold and 6.75-fold, respectively. Overall, these findings demonstrated that P. plecoglossicida causes profound disruption of central energy metabolism in large yellow croakers and induces hypoglycemia, with activation of the glycogen shunt closely associated with survival.