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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Colibactin in avian pathogenic Escherichia coli contributes to the development of meningitis in a mouse model
Peili Wang1,2, Jiaxiang Zhang1,2, Yanfei Chen1,2
1College of Veterinary Medicine, Yangzhou University; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou.
Abstract:
Colibactin is synthesized by a 54-kb genomic island, leads to toxicity in eukaryotic cells, and plays a vital role in many diseases, including neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is speculated to be an armory of extraintestinal pathogenic Escherichia coli and can be a potential zoonotic bacterium that threatens human and animal health. In this study, the APEC XM meningitis mouse model was successfully established to investigate the effect of colibactin in in vivo infection. The clbH-deletion mutant strain induced lower γ-H2AX expression, no megalocytosis, and no cell cycle arrest in bEnd.3 cells, which showed that the deletion of clbH decreased the production of colibactin in the APEC XM strain. The deletion of clbH did not affect the APEC XM strain's ability of adhering to and invading bEnd.3 cells. In vitro, the non-colibactin-producing strain displayed significantly lower serum resistance and it also induced a lower level of cytokine mRNA and few disruptions of tight junction proteins in infected bEnd.3 cells. Meningitis did not occur in APEC ΔclbH-infected mice in vivo, who showed fewer clinical symptoms and fewer lesions on radiological and histopathological analyses. Compared with the APEX XM strain, APEC ΔclbH induced lower bacterial colonization in tissues, lower mRNA expression of cytokines in brain tissues, and slight destruction of the brain blood barrier. These results indicate that clbH is a necessary component for the synthesis of genotoxic colibactin, and colibactin is related to the development of meningitis induced by APEC XM.
Insights
Colibactin, a toxin produced by Escherichia coli, causes cell damage and is linked to meningitis. Deleting the clbH gene in avian pathogenic E. coli (APEC) significantly reduced colibactin production and prevented meningitis in mice.
Area of Science:
- Microbiology
- Pathogenesis
- Genomics
Background:
- Colibactin, a genotoxin synthesized by a 54-kb genomic island, contributes to eukaryotic cell toxicity and diseases like neonatal sepsis and meningitis.
- Avian pathogenic Escherichia coli (APEC) is an extraintestinal pathogenic E. coli with zoonotic potential, posing risks to human and animal health.
Purpose of the Study:
- To investigate the role of colibactin in APEC-induced meningitis using a mouse model.
- To determine the necessity of the clbH gene in colibactin synthesis and its impact on APEC virulence.
Main Methods:
- Established an APEC XM meningitis mouse model for in vivo infection studies.
- Created a clbH-deletion mutant strain (APEC ΔclbH) to assess colibactin production and virulence.
- Evaluated bacterial adherence, invasion, serum resistance, cytokine expression, tight junction disruption, and host tissue damage in vitro and in vivo.
Main Results:
- Deletion of clbH in APEC XM significantly reduced colibactin production, evidenced by lower γ-H2AX expression and absence of megalocytosis and cell cycle arrest in vitro.
- The clbH deletion did not affect APEC's adherence or invasion capabilities but decreased serum resistance.
- APEC ΔclbH infection in mice resulted in no meningitis, fewer clinical symptoms, reduced lesions, lower bacterial colonization, decreased cytokine expression in brain tissue, and less BBB disruption compared to the wild-type APEC XM.
Conclusions:
- The clbH gene is essential for the synthesis of genotoxic colibactin in APEC XM.
- Colibactin plays a critical role in the development of meningitis induced by APEC XM, contributing to virulence and host tissue damage.
