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SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis

Streptococcus suis (S. suis) is one of the important pathogens that cause bacterial meningitis in pigs and humans. Evading host immune defences and penetrating the blood-brain barrier (BBB) are the preconditions for S. suis to cause meningitis, while the underlying mechanisms during these pathogenic...

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Autores principales: Pan, Zihao, He, Peijuan, Zhang, Yue, Gu, Qibing, Chen, Shengsheng, Yu, Yong, Shao, Jing, Wang, Kaicheng, Wu, Zongfu, Yao, Huochun, Ma, Jiale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337661/
https://www.ncbi.nlm.nih.gov/pubmed/35853077
http://dx.doi.org/10.1371/journal.ppat.1010710
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author Pan, Zihao
He, Peijuan
Zhang, Yue
Gu, Qibing
Chen, Shengsheng
Yu, Yong
Shao, Jing
Wang, Kaicheng
Wu, Zongfu
Yao, Huochun
Ma, Jiale
author_facet Pan, Zihao
He, Peijuan
Zhang, Yue
Gu, Qibing
Chen, Shengsheng
Yu, Yong
Shao, Jing
Wang, Kaicheng
Wu, Zongfu
Yao, Huochun
Ma, Jiale
author_sort Pan, Zihao
collection PubMed
description Streptococcus suis (S. suis) is one of the important pathogens that cause bacterial meningitis in pigs and humans. Evading host immune defences and penetrating the blood-brain barrier (BBB) are the preconditions for S. suis to cause meningitis, while the underlying mechanisms during these pathogenic processes are not fully understood. By detecting the red blood and white blood cells counts, IL-8 expression, and the pathological injury of brain in a mouse infection model, a serine-rich repeat (SRR) glycoprotein, designated as SssP1, was identified as a critical facilitator in the process of causing meningitis in this study. SssP1 was exported to assemble a fimbria-like component, thus contributed to the bacterial adhesion to and invasion into human brain microvascular endothelial cells (HBMECs), and activates the host inflammatory response during meningitis but is not involved in the actin cytoskeleton rearrangement and the disruption of tight junctions. Furthermore, the deletion of sssP1 significantly attenuates the ability of S. suis to traverse the BBB in vivo and in vitro. A pull-down analysis identified vimentin as the potential receptors of SssP1 during meningitis and following Far-Western blot results confirmed this ligand-receptor binding mediated by the NR2 (the second nonrepeat region) region of SssP1. The co-localisation of vimentin and S. suis observed by laser scanning confocal microscopy with multiplex fluorescence indicated that vimentin significantly enhances the interaction between SssP1 and BBB. Further study identified that the NR(216-781) and NR(1711-2214) fragments of SssP1 play critical roles to bind to the BBB depending on the sialylation of vimentin, and this binding is significantly attenuated when the antiserum of NR(216-781) or NR(1711-2214) blocked the bacterial cells, or the vimentin antibody blocked the BBB. Similar binding attenuations are observed when the bacterial cells were preincubated with the vimentin, or the BBB was preincubated with the recombinant protein NR(216-781), NR(1711-2214) or sialidase. In conclusion, these results reveal a novel receptor-ligand interaction that enhances adhesion to and penetration of the BBB to cause bacterial meningitis in the S. suis infection and highlight the importance of vimentin in host-pathogen interactions.
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spelling pubmed-93376612022-07-30 SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis Pan, Zihao He, Peijuan Zhang, Yue Gu, Qibing Chen, Shengsheng Yu, Yong Shao, Jing Wang, Kaicheng Wu, Zongfu Yao, Huochun Ma, Jiale PLoS Pathog Research Article Streptococcus suis (S. suis) is one of the important pathogens that cause bacterial meningitis in pigs and humans. Evading host immune defences and penetrating the blood-brain barrier (BBB) are the preconditions for S. suis to cause meningitis, while the underlying mechanisms during these pathogenic processes are not fully understood. By detecting the red blood and white blood cells counts, IL-8 expression, and the pathological injury of brain in a mouse infection model, a serine-rich repeat (SRR) glycoprotein, designated as SssP1, was identified as a critical facilitator in the process of causing meningitis in this study. SssP1 was exported to assemble a fimbria-like component, thus contributed to the bacterial adhesion to and invasion into human brain microvascular endothelial cells (HBMECs), and activates the host inflammatory response during meningitis but is not involved in the actin cytoskeleton rearrangement and the disruption of tight junctions. Furthermore, the deletion of sssP1 significantly attenuates the ability of S. suis to traverse the BBB in vivo and in vitro. A pull-down analysis identified vimentin as the potential receptors of SssP1 during meningitis and following Far-Western blot results confirmed this ligand-receptor binding mediated by the NR2 (the second nonrepeat region) region of SssP1. The co-localisation of vimentin and S. suis observed by laser scanning confocal microscopy with multiplex fluorescence indicated that vimentin significantly enhances the interaction between SssP1 and BBB. Further study identified that the NR(216-781) and NR(1711-2214) fragments of SssP1 play critical roles to bind to the BBB depending on the sialylation of vimentin, and this binding is significantly attenuated when the antiserum of NR(216-781) or NR(1711-2214) blocked the bacterial cells, or the vimentin antibody blocked the BBB. Similar binding attenuations are observed when the bacterial cells were preincubated with the vimentin, or the BBB was preincubated with the recombinant protein NR(216-781), NR(1711-2214) or sialidase. In conclusion, these results reveal a novel receptor-ligand interaction that enhances adhesion to and penetration of the BBB to cause bacterial meningitis in the S. suis infection and highlight the importance of vimentin in host-pathogen interactions. Public Library of Science 2022-07-19 /pmc/articles/PMC9337661/ /pubmed/35853077 http://dx.doi.org/10.1371/journal.ppat.1010710 Text en © 2022 Pan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pan, Zihao
He, Peijuan
Zhang, Yue
Gu, Qibing
Chen, Shengsheng
Yu, Yong
Shao, Jing
Wang, Kaicheng
Wu, Zongfu
Yao, Huochun
Ma, Jiale
SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title_full SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title_fullStr SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title_full_unstemmed SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title_short SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
title_sort sssp1, a fimbria-like component of streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337661/
https://www.ncbi.nlm.nih.gov/pubmed/35853077
http://dx.doi.org/10.1371/journal.ppat.1010710
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