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

Bacterial sepsis-induced hypoglycemia is associated with increased mortality. In this study, the large yellow croakers injected with PBS served as the control group (CG), while those injected with an equivalent dose of P. plecoglossicida were categorized into moribund group (MG) or survival group (SG), based on their post-infection status.. The results showed that P. plecoglossicida depleted hepatic glycogen in all infected croakers, but only moribund groups showed decreased blood glucose (0.80 mmol/L). Infection also led to the accumulation of lipid peroxides (LPO), a reduction in reduced glutathione (GSH), and a decreased NAD+/NADH. However, these fluctuations were significantly milder in the SG compared to the MG. Besides, the MG also exhibited reduction in intermediates of glycolysis, TCA cycle, oxidative phosphorylation, and decreased of glycerides and fatty acids, along with mitochondrial swelling and cristae disappearance, as well as downregulation of G6pc. The SG group exhibited alterations in 26 lipid species (18 increased and 8 decreased) and 13 carbohydrates (9 increased and 4 decreased). Among these substances, the most pronounced fluctuations were observed in the glycogen shunt products: maltose (47.78-fold vs CG, 7995-fold vs MG) and D-(+)-trehalose (964.08-fold vs CG, 1106.38-fold vs MG). Additionally, we identified pptse6 (ACRRS2_13720), a effector of type Ⅵ secretion system (T6SS), as a key virulence gene in P. plecoglossicida, whose absence reduced bacterial virulence by 808-fold. Another competitive T6SS effector, TreS, is involved in the synthesis of maltose and D-(+)-trehalose. Its deletion resulted in a 7.75-fold reduction in maltose production and a 6.75-fold decrease in trehalose synthesis. In conclusion, P. plecoglossicida caused energy metabolism disorder in croakers, with induced hypoglycemia, while glycogen shunt is related to survival.