RyhB in Avian Pathogenic Escherichia coli Regulates the Expression of Virulence-Related Genes and Contributes to Meningitis Development in a Mouse Model

• Published in: International journal of molecular sciences 2022-12, Vol.23 (24), p.15532
• Main Authors: Meng, Xia, Chen, Yanfei, Wang, Peili, He, Mengping, Shi, Yuxing, Lai, Yuxin, Zhu, Guoqiang, Wang, Heng
• Format: Article
• Language: English
• Subjects: Adhesion; Animals; APEC; Bacteria; Biofilms; Biosynthesis; Birds - metabolism; Blood-brain barrier; Brain damage; Chickens - metabolism; Deletion mutant; Diarrhea; E coli; Endothelial cells; Endothelial Cells - metabolism; Escherichia coli; Escherichia coli - metabolism; Escherichia coli Infections - microbiology; Escherichia coli Proteins - metabolism; Gene expression; Genes; Genomes; Homeostasis; IL-1β; Interleukin 6; Membrane permeability; Meningitis; meningitis development; Metabolism; Mice; Microvasculature; Mutants; Neonates; Pathogenesis; Pathogenicity; Poultry Diseases - microbiology; RyhB; Signal transduction; Tumor necrosis factor-α; Virulence; Virulence - genetics; Virulence Factors - genetics; Virulence Factors - metabolism; virulence regulation; Zonula occludens-1 protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232415532

Avian pathogenic (APEC) is an important member of extraintestinal pathogenic (ExPEC). It shares similar pathogenic strategies with neonatal meningitis (NMEC) and may threaten human health due to its potential zoonosis. RyhB is a small non-coding RNA that regulates iron homeostasis in . However, it is unclear whether RyhB regulates meningitis occurrence. To investigate the function of RyhB in the development of meningitis, we constructed the deletion mutant APEC XM∆ and the complemented mutant APEC XM∆ /p , established a mouse meningitis model and evaluated the role of RyhB in virulence of APEC. The results showed that the deletion of decreased biofilm formation, adhesion to the brain microvascular endothelial cell line bEnd.3 and serum resistance. RNA-seq data showed that the expression of multiple virulence-related genes changed in the deletion mutant in the presence of duck serum. Deletion of reduced the clinical symptoms of mice, such as opisthotonus, diarrhea and neurological signs, when challenged with APEC. Compared with the mice infected with the wild-type APEC, fewer histopathological lesions were observed in the brain of mice infected with the deletion mutant APEC XM∆ . The bacterial loads in the tissues and the relative expression of cytokines ( , , and ) in the brain significantly decreased when challenged with the APEC XM∆ . The expressions of tight junction proteins (claudin-5, occludin and ZO-1) were not reduced in the brain of mice infected with APEC XM∆ ; that is, the blood-brain barrier permeability of mice was not significantly damaged. In conclusion, RyhB contributes to the pathogenicity of APEC XM in the meningitis-causing process by promoting biofilm formation, adhesion to endothelial cells, serum resistance and virulence-related genes expression.