PurA facilitates Edwardsiella piscicida to escape NF-KB signaling activation

The host NF-KB 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-KB signaling remains largely unknown. Herein, using E. piscicida transposon insertion mutant library combined with a NF-KB luciferase reporter system, we identified forty-six genes of E. piscicida, which were involved in inhibiting the NF-KB 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-KB activation in vivo. Specifically, we identified the adenylosuccinate synthase mutated strain (Delta purA) infection exhibited a robust activation of NF-KB 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-KB activation, which will contribute to better understanding the pathogenesis of this important pathogen.