2. Academic Validation
  3. Occludin and collagen IV degradation mediated by the T9SS effector SspA contributes to blood-brain barrier damage in ducks during Riemerella anatipestifer infection

Occludin and collagen IV degradation mediated by the T9SS effector SspA contributes to blood-brain barrier damage in ducks during Riemerella anatipestifer infection

  • Vet Res. 2024 Apr 9;55(1):49. doi: 10.1186/s13567-024-01304-y.
Zongchao Chen 1 2,  Min Zhu 2,  Dan Liu 2,  Mengsi Wu 2,  Pengfei Niu 2,  Yang Yu 1,  Chan Ding 3,  Shengqing Yu 4 5 6
Affiliations

Affiliations

  • 1 Jiangsu Agri-Animal Husbandry Vocational College, Veterinary Bio-Pharmaceutical, Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals, Taizhou, Jiangsu, China.
  • 2 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China.
  • 3 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China. shoveldeen@shvri.ac.cn.
  • 4 Jiangsu Agri-Animal Husbandry Vocational College, Veterinary Bio-Pharmaceutical, Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals, Taizhou, Jiangsu, China. Yu_20220209@163.com.
  • 5 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China. Yu_20220209@163.com.
  • 6 Yangzhou You-Jia-Chuang Biotechnology Co., Ltd., Yangzhou, China. Yu_20220209@163.com.
PMID: 38594770 DOI: 10.1186/s13567-024-01304-y
Abstract

Riemerella anatipestifer Infection is characterized by meningitis with neurological symptoms in ducklings and has adversely affected the poultry industry. R. anatipestifer strains can invade the duck brain to cause meningitis and neurological symptoms, but the underlying mechanism remains unknown. In this study, we showed that obvious clinical symptoms, an increase in blood‒brain barrier (BBB) permeability, and the accumulation of inflammatory cytokines occurred after intravenous Infection with the Yb2 strain but not the mutant strain Yb2ΔsspA, indicating that Yb2 Infection can lead to cerebrovascular dysfunction and that the type IX secretion system (T9SS) effector SspA plays a critical role in this pathological process. In addition, we showed that Yb2 Infection led to rapid degradation of occludin (a tight junction protein) and collagen IV (a basement membrane protein), which contributed to endothelial barrier disruption. The interaction between SspA and occludin was confirmed by coimmunoprecipitation. Furthermore, we found that SspA was the main Enzyme mediating occludin and collagen IV degradation. These data indicate that R. anatipestifer SspA mediates occludin and collagen IV degradation, which functions in BBB disruption in R. anatipestifer-infected ducks. These findings establish the molecular mechanisms by which R. anatipestifer targets duckling endothelial cell junctions and provide new perspectives for the treatment and prevention of R. anatipestifer Infection.

Keywords

Riemerella anatipestifer; SspA; T9SS; blood‒brain barrier; collagen IV; occludin.

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