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HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule
Streptococcus suis 2 (SS2) is an important zoonotic pathogen that substantially harms the swine industry and poses threats to human health. Excessive inflammation is considered to be a hallmark of SS2 infection because it is responsible for most clinical signs of SS2, especially streptococcal toxic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920816/ https://www.ncbi.nlm.nih.gov/pubmed/31684161 http://dx.doi.org/10.3390/microorganisms7110522 |
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author | Liu, Liang Zhang, Qiang Xu, Zhongmin Huang, Jingjing Zhu, Weifeng Zhang, Anding Sun, Xiaomei Jin, Meilin |
author_facet | Liu, Liang Zhang, Qiang Xu, Zhongmin Huang, Jingjing Zhu, Weifeng Zhang, Anding Sun, Xiaomei Jin, Meilin |
author_sort | Liu, Liang |
collection | PubMed |
description | Streptococcus suis 2 (SS2) is an important zoonotic pathogen that substantially harms the swine industry and poses threats to human health. Excessive inflammation is considered to be a hallmark of SS2 infection because it is responsible for most clinical signs of SS2, especially streptococcal toxic shock-like syndrome. However, the current knowledge of SS2-induced excessive inflammation remains limited. In this study, we identified HP1717 as a novel extracellular pro-inflammatory protein in SS2 that can induce robust expression of inflammatory cytokines in RAW264.7 macrophages. Notably, the pro-inflammatory ability of HP1717 was dose-dependent and heat-sensitive, and it required the recognition of Toll-like receptor 2 (TLR2) and the phosphorylation of both extracellular signal-regulated kinases 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Further, by constructing a deletion mutant, we demonstrated that HP1717 significantly influenced the biosynthesis of the bacterial capsule, which plays a critical role in the virulence of SS2 by interfering with the ability of host immune cells to phagocytize and kill the pathogen. Indeed, the mutant strain displayed reduced resistance to whole-blood killing compared with the wild strain. Finally, murine experiments indicated that the deletion of hp1717 in SS2 reduced the lethality, pro-inflammatory activity, and bacterial loads in mice. Collectively, our data reveal HP1717 as a novel virulence-related factor of SS2 that can induce an excessive inflammatory response and significantly affect the bacterial capsule, thus expanding our understanding of the pathogenesis of S. suis. |
format | Online Article Text |
id | pubmed-6920816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69208162019-12-24 HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule Liu, Liang Zhang, Qiang Xu, Zhongmin Huang, Jingjing Zhu, Weifeng Zhang, Anding Sun, Xiaomei Jin, Meilin Microorganisms Article Streptococcus suis 2 (SS2) is an important zoonotic pathogen that substantially harms the swine industry and poses threats to human health. Excessive inflammation is considered to be a hallmark of SS2 infection because it is responsible for most clinical signs of SS2, especially streptococcal toxic shock-like syndrome. However, the current knowledge of SS2-induced excessive inflammation remains limited. In this study, we identified HP1717 as a novel extracellular pro-inflammatory protein in SS2 that can induce robust expression of inflammatory cytokines in RAW264.7 macrophages. Notably, the pro-inflammatory ability of HP1717 was dose-dependent and heat-sensitive, and it required the recognition of Toll-like receptor 2 (TLR2) and the phosphorylation of both extracellular signal-regulated kinases 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Further, by constructing a deletion mutant, we demonstrated that HP1717 significantly influenced the biosynthesis of the bacterial capsule, which plays a critical role in the virulence of SS2 by interfering with the ability of host immune cells to phagocytize and kill the pathogen. Indeed, the mutant strain displayed reduced resistance to whole-blood killing compared with the wild strain. Finally, murine experiments indicated that the deletion of hp1717 in SS2 reduced the lethality, pro-inflammatory activity, and bacterial loads in mice. Collectively, our data reveal HP1717 as a novel virulence-related factor of SS2 that can induce an excessive inflammatory response and significantly affect the bacterial capsule, thus expanding our understanding of the pathogenesis of S. suis. MDPI 2019-11-03 /pmc/articles/PMC6920816/ /pubmed/31684161 http://dx.doi.org/10.3390/microorganisms7110522 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Liang Zhang, Qiang Xu, Zhongmin Huang, Jingjing Zhu, Weifeng Zhang, Anding Sun, Xiaomei Jin, Meilin HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title | HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title_full | HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title_fullStr | HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title_full_unstemmed | HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title_short | HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule |
title_sort | hp1717 contributes to streptococcus suis virulence by inducing an excessive inflammatory response and influencing the biosynthesis of the capsule |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920816/ https://www.ncbi.nlm.nih.gov/pubmed/31684161 http://dx.doi.org/10.3390/microorganisms7110522 |
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