PhoP/PhoQ Two-Component System Contributes to Intestinal Inflammation Induced by Cronobacter sakazakii in Neonatal Mice.

Cronobacter sakazakii ( C. sakazakii ) is a foodborne pathogen capable of causing severe infections in newborns. The PhoP/PhoQ two-component system exerts a significant influence on bacterial virulence. This study aimed to investigate the impact of the PhoP/PhoQ system on intestinal inflammation in neonatal mice induced by C. sakazakii . Neonatal mice were infected orally by C. sakazakii BAA-894 (WT), a phoPQ -gene-deletion strain (Δ phoPQ ), and a complementation strain (Δ phoPQ C ), and the intestinal inflammation in the mice was monitored. Deletion of the phoPQ gene reduced the viable count of C. sakazakii in the ileum and alleviated intestinal tissue damage. Moreover, caspase-3 activity in the ileum of the WT- and Δ phoPQ C -infected mice was significantly elevated compared to that of the Δ phoPQ and control groups. ELISA results showed elevated levels of TNF-α and IL-6 in the ileum of the mice infected with WT and Δ phoPQ C . In addition, deletion of the phoPQ gene in C. sakazakii resulted in a down-regulation of inflammatory genes (IL-1β, TNF-α, IL-6, NF-κB p65, TLR4) within the ileum and decreased inflammation by modulating the TLR4/NF-κB pathway. It is suggested that targeting the PhoP/PhoQ two-component system could be a potential strategy for mitigating C. sakazakii -induced neonatal infections.