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Published on: November 5, 2019
ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model
Peili Wang1,2, Jiaxiang Zhang1,2, Yanfei Chen1,2
1College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Abstract:
Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the poultry industry and may threaten human health due to its potential zoonosis. In this study, we confirmed that clbG was necessary for the APEC XM strain to produce colibactin. The deletion of clbG on APEC XM contributed to lowered γH2AX expression, no megalocytosis, and no cell cycle arrest in vitro. None of the 4-week Institute of Cancer Research mice infected with the APEC XM ΔclbG contracted meningitis or displayed weakened clinical symptoms. Fewer histopathological lesions were observed in the APEC XM ΔclbG group. The bacterial colonization of tissues and the relative expression of cytokines (IL-1β, IL-6, and TNF-α) in the brains decreased significantly in the APEC XM ΔclbG group compared to those in the APEC XM group. The tight junction proteins (claudin-5, occludin, and ZO-1) were not significantly destroyed in APEC XM ΔclbG group in vivo and in vitro. In conclusion, clbG is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice.
Insights
The gene clbG is essential for producing the genotoxin colibactin in avian pathogenic Escherichia coli (APEC). Deleting clbG reduced APEC
Area of Science:
- Microbiology
- Molecular Biology
- Pathogen Research
Background:
- Colibactin, a genotoxin, disrupts eukaryotic cell cycles and is implicated in diseases like neonatal sepsis and meningitis.
- Avian pathogenic Escherichia coli (APEC) causes poultry diseases and poses zoonotic risks.
- Understanding APEC virulence factors is crucial for animal and human health.
Purpose of the Study:
- To investigate the role of the gene clbG in colibactin production by APEC.
- To evaluate the impact of clbG deletion on APEC virulence and pathogenicity in vitro and in vivo.
Main Methods:
- Deletion of the clbG gene in the APEC XM strain.
- In vitro assays assessing genotoxicity, megalocytosis, and cell cycle arrest.
- In vivo infection model using Institute of Cancer Research mice to evaluate meningitis, clinical symptoms, histopathology, bacterial colonization, cytokine expression, and tight junction integrity.
Main Results:
- Deletion of clbG abolished colibactin production in APEC XM.
- APEC XM ΔclbG showed reduced genotoxicity, no megalocytosis, and no cell cycle arrest in vitro.
- Mice infected with APEC XM ΔclbG exhibited significantly reduced meningitis, fewer lesions, lower bacterial colonization, and decreased pro-inflammatory cytokine expression compared to the wild-type APEC XM group.
Conclusions:
- The clbG gene is indispensable for colibactin synthesis in APEC.
- clbG deletion attenuates APEC virulence and pathogenicity, significantly reducing its ability to cause meningitis in a mouse model.
- Targeting clbG could be a potential strategy to control APEC infections.
