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Published on: February 19, 2013
PhoP/PhoQ Two-Component System Contributes to Intestinal Inflammation Induced by Cronobacter sakazakii in Neonatal
Yan Ma1, Yingying Zhang2, Yuting Wang1
1School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian 463000, China.
Insights
Targeting the PhoP/PhoQ system in Cronobacter sakazakii (C. sakazakii) reduces intestinal inflammation and tissue damage in neonatal mice. This finding suggests a potential strategy for mitigating C. sakazakii infections in newborns.
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Cronobacter sakazakii (C. sakazakii) is a foodborne pathogen causing severe neonatal infections.
- The bacterial PhoP/PhoQ two-component system is crucial for virulence.
- Understanding its role in intestinal inflammation is vital for developing interventions.
Purpose of the Study:
- To investigate the impact of the PhoP/PhoQ system on C. sakazakii-induced intestinal inflammation in neonatal mice.
- To determine the role of PhoP/PhoQ in bacterial survival and host immune response.
- To explore potential therapeutic targets for C. sakazakii infections.
Main Methods:
- Oral infection of neonatal mice with wild-type C. sakazakii, a phoPQ-deletion mutant, and a complemented strain.
- Monitoring of intestinal inflammation, bacterial counts in the ileum, and caspase-3 activity.
- ELISA analysis of inflammatory cytokines (TNF-α, IL-6) and gene expression profiling of inflammatory markers.
Main Results:
- Deletion of the phoPQ gene significantly reduced C. sakazakii viable counts and alleviated intestinal tissue damage.
- Caspase-3 activity and levels of TNF-α and IL-6 were elevated in mice infected with wild-type C. sakazakii compared to the mutant.
- The phoPQ deletion down-regulated inflammatory genes (IL-1β, TNF-α, IL-6, NF-κB p65, TLR4) and modulated the TLR4/NF-κB pathway.
Conclusions:
- The PhoP/PhoQ system is a key virulence factor for C. sakazakii in neonatal intestinal infection.
- Targeting the PhoP/PhoQ system can attenuate C. sakazakii-induced intestinal inflammation.
- Modulating the PhoP/PhoQ system presents a promising strategy for treating C. sakazakii infections in newborns.
Abstract:
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 (ΔphoPQ), and a complementation strain (ΔphoPQ), 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 ΔphoPQ-infected mice was significantly elevated compared to that of the ΔphoPQ and control groups. ELISA results showed elevated levels of TNF-α and IL-6 in the ileum of the mice infected with WT and ΔphoPQ. 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.
