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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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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
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author Fan, Yu
Sun, Hongmin
Yang, Wen
Bai, Jing
Liu, Peng
Huang, Min
Guo, Xi
Yang, Bin
Feng, Lu
author_facet Fan, Yu
Sun, Hongmin
Yang, Wen
Bai, Jing
Liu, Peng
Huang, Min
Guo, Xi
Yang, Bin
Feng, Lu
author_sort Fan, Yu
collection PubMed
description 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.
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spelling pubmed-91417472022-05-28 YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis Fan, Yu Sun, Hongmin Yang, Wen Bai, Jing Liu, Peng Huang, Min Guo, Xi Yang, Bin Feng, Lu Int J Mol Sci Article 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. MDPI 2022-05-16 /pmc/articles/PMC9141747/ /pubmed/35628353 http://dx.doi.org/10.3390/ijms23105543 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fan, Yu
Sun, Hongmin
Yang, Wen
Bai, Jing
Liu, Peng
Huang, Min
Guo, Xi
Yang, Bin
Feng, Lu
YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title_full YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title_fullStr YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title_full_unstemmed YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title_short YbdO Promotes the Pathogenicity of Escherichia coli K1 by Regulating Capsule Synthesis
title_sort ybdo promotes the pathogenicity of escherichia coli k1 by regulating capsule synthesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141747/
https://www.ncbi.nlm.nih.gov/pubmed/35628353
http://dx.doi.org/10.3390/ijms23105543
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