RyhB in Avian Pathogenic <i>Escherichia coli</i> Regulates the Expression of Virulence-Related Genes and Contributes to Meningitis Development in a Mouse Model
Avian pathogenic <i>Escherichia coli</i> (APEC) is an important member of extraintestinal pathogenic <i>Escherichia coli</i> (ExPEC). It shares similar pathogenic strategies with neonatal meningitis <i>E. coli</i> (NMEC) and may threaten human health due to its po...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15532 |
| Summary: | Avian pathogenic <i>Escherichia coli</i> (APEC) is an important member of extraintestinal pathogenic <i>Escherichia coli</i> (ExPEC). It shares similar pathogenic strategies with neonatal meningitis <i>E. coli</i> (NMEC) and may threaten human health due to its potential zoonosis. RyhB is a small non-coding RNA that regulates iron homeostasis in <i>E. coli</i>. 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∆<i>ryhB</i> and the complemented mutant APEC XM∆<i>ryhB</i>/p<i>ryhB</i>, established a mouse meningitis model and evaluated the role of RyhB in virulence of APEC. The results showed that the deletion of <i>ryhB</i> 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 <i>ryhB</i> deletion mutant in the presence of duck serum. Deletion of <i>ryhB</i> 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 <i>ryhB</i> deletion mutant APEC XM∆<i>ryhB</i>. The bacterial loads in the tissues and the relative expression of cytokines (<i>IL-1β</i>, <i>IL-6</i>, and <i>TNF-α</i>) in the brain significantly decreased when challenged with the APEC XM∆<i>ryhB</i>. The expressions of tight junction proteins (claudin-5, occludin and ZO-1) were not reduced in the brain of mice infected with APEC XM∆<i>ryhB</i>; 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. |
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| ISSN: | 1661-6596 1422-0067 |