fliC Mediates Pseudomonas plecoglossicida’s Hijack of Inflammatory Immunity and Glucose Metabolism in the Large Yellow Croaker

The bacterial flagellum plays a crucial role in pathogenesis. However, the mechanism by which the flagellum interferes with host energy metabolism remains unclear. In this study, we confirmed that deletion of the <i>fliC</i> gene resulted in a 30% reduction in the virulence of <i>Pseudomonas plecoglossicida</i> against the large yellow croaker (<i>Larimichthys crocea</i>). Compared to the wild-type strain (WT) infection group, the Δ<i>fliC</i> infection group exhibited a 29.54% decrease in the number of vacuolar degeneration hepatocytes and a 50.83% higher liver glycogen content. Furthermore, infection led to decreased mitochondrial complex V activity, a reduced NAD+/NADH ratio, lower levels of reduced glutathione (GSH), and increased lipid peroxide levels; however, these metabolic perturbations were significantly ameliorated in the Δ<i>fliC</i> group compared to the WT group. Proteomic analysis revealed that the dysregulation of the complement cascade and core carbon metabolic pathways observed in the WT infection group liver was significantly alleviated in the Δ<i>fliC</i> infection group. Additionally, in the Δ<i>fliC</i> infection group, pro-inflammatory genes (such as <i>Tlr5</i>, <i>Tnfα</i>, and <i>Il1β</i>) were downregulated, while lipid metabolism-related genes (such as <i>Acox1</i>, <i>Cpt1a</i>, and <i>Pparα</i>) were upregulated, suggesting the suppression of the Tlr5/NF-κB immune signaling axis and enhanced fatty acid <i>β</i>-oxidation. Collectively, <i>fliC</i> may mediate the disruption of host glucose and lipid metabolism homeostasis through a Tlr5-triggered immunometabolic regulatory axis. In conclusion, this study demonstrates that bacterial flagella modulate host energy metabolism, expanding our understanding of flagellum-mediated pathogenesis.