Abstract

The host NF-κB signaling pathway plays critical role in defensing against bacterial infection. However, bacteria also evolve strategies to escape from host clearance. Edwardsiella piscicida is a threatening pathogen in aquaculture, while the molecular mechanism of E. piscicida in inhibiting NF-κB signaling remains largely unknown. Herein, using E. piscicida transposon insertion mutant library combined with a NF-κB luciferase reporter system, we identified forty-six genes of E. piscicida , which were involved in inhibiting the NF-κB signaling activation in vitro . Moreover, we further explored the top 10 significantly changed mutants through zebrafish larvae infection model and validated that six genes were involved in inhibiting NF-κB activation in vivo . Specifically, we identified the adenylosuccinate synthase mutated strain ( ΔpurA ) infection exhibited a robust activation of NF-κB signaling, along with higher expression of cxcl8a and cxcl8b to mediate the recruitment of neutrophils in vivo . Taken together, these results identified the key factors of E. piscicida in inhibiting NF-κB activation, which will contribute to better understanding the pathogenesis of this important pathogen.