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YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis

Escherichia coli K1 is the most popular neonatal meningitis-causing Gram-negative bacterium. As a key virulence determinant, the K1 capsule enhances the survival of E. coli K1 in human brain microvascular endothelial cells (HBMECs) upon crossing the blood–brain barrier; however, the regulatory mecha...

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Detalles Bibliográficos
Autores principales: Fan, Yu, Sun, Hongmin, Yang, Wen, Bai, Jing, Liu, Peng, Huang, Min, Guo, Xi, Yang, Bin, Feng, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141747/
https://www.ncbi.nlm.nih.gov/pubmed/35628353
http://dx.doi.org/10.3390/ijms23105543
Descripción
Sumario:Escherichia coli K1 is the most popular neonatal meningitis-causing Gram-negative bacterium. As a key virulence determinant, the K1 capsule enhances the survival of E. coli K1 in human brain microvascular endothelial cells (HBMECs) upon crossing the blood–brain barrier; however, the regulatory mechanisms of capsule synthesis during E. coli K1 invasion of HBMECs remain unclear. Here, we identified YbdO as a transcriptional regulator that promotes E. coli K1 invasion of HBMECs by directly activating K1 capsule gene expression to increase K1 capsule synthesis. We found that ybdO deletion significantly reduced HBMEC invasion by E. coli K1 and meningitis occurrence in mice. Additionally, electrophoretic mobility shift assay and chromatin immunoprecipitation–quantitative polymerase chain reaction analysis indicated that YbdO directly activates kpsMT and neuDBACES expression, which encode products involved in K1 capsule transport and synthesis by directly binding to the kpsM promoter. Furthermore, ybdO transcription was directly repressed by histone-like nucleoid structuring protein (H-NS), and we observed that acidic pH similar to that of early and late endosomes relieves this transcriptional repression. These findings demonstrated the regulatory mechanism of YbdO on K1 capsule synthesis, providing further insights into the evolution of E. coli K1 pathogenesis and host–pathogen interaction.