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Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model
Published on: July 1, 2018
Evaluation of the pathogenesis of meningitis caused by Streptococcus suis sequence type 7 using the infection of BV2
Han Zheng1, Hui Sun1, Maria de la Cruz Dominguez-Punaro2
1State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, PR China.
Abstract:
Streptococcus suis is an important agent of swine and human meningitis. Among several sequence types (STs) characterized within the S. suis strain population, ST7 has emerged only in China and has been reported to be the cause of the human outbreak caused by S. suis in 2005. S. suis ST7 was shown to be derived from S. suis ST1 through a single-nucleotide change in the housekeeping gene thyA. The virulence potential of S. suis ST7 is reported to be higher than that of the worldwide-studied pathogenic S. suis ST1. The pathogenesis of ST1 infection has been partially elucidated, but information on the pathogenesis of ST7 infections remains scarce. To improve our understanding of the mechanisms involved in the development of meningitis caused by ST7, this study compared the microglial inflammatory response induced by ST1 and ST7 strains. The data showed that S. suis ST7 possessed a higher ability to induce pro-inflammatory cytokine production and to activate mitogen-activated protein kinase pathways and several transcription factors. The stimulation of microglial cells by S. suis increased the expression levels of the nucleotide oligomerization domain 2 (Nod2) gene. Finally, the results indicated that signal transducer and activator of transcription 3 (STAT-3) was involved in the development of meningitis induced by S. suis ST7 infection.
Insights
Streptococcus suis ST7 causes more severe meningitis than ST1 by increasing inflammatory responses. This study reveals ST7
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Streptococcus suis is a significant cause of meningitis in both pigs and humans.
- Sequence Type 7 (ST7) of S. suis, originating in China, caused a human outbreak in 2005 and shows higher virulence than the globally prevalent ST1.
- The pathogenesis of S. suis ST7 meningitis remains poorly understood compared to ST1.
Purpose of the Study:
- To elucidate the pathogenic mechanisms of Streptococcus suis ST7 by comparing its induced microglial inflammatory response with that of S. suis ST1.
- To identify key molecular pathways and factors involved in ST7-induced meningitis.
Main Methods:
- Comparative analysis of microglial inflammatory responses to S. suis ST1 and ST7 strains.
- Measurement of pro-inflammatory cytokine production.
- Assessment of mitogen-activated protein kinase (MAPK) pathway activation.
- Evaluation of transcription factor activity and gene expression, including Nod2 and STAT-3.
Main Results:
- S. suis ST7 demonstrated a significantly higher capacity to induce pro-inflammatory cytokine production compared to ST1.
- ST7 activated MAPK pathways and several transcription factors more robustly than ST1.
- Microglial stimulation by S. suis led to increased expression of the Nucleotide Oligomerization Domain 2 (Nod2) gene.
- Signal Transducer and Activator of Transcription 3 (STAT-3) was identified as a crucial factor in the development of ST7-induced meningitis.
Conclusions:
- Streptococcus suis ST7 exhibits enhanced virulence in inducing microglial inflammatory responses, contributing to meningitis pathogenesis.
- The activation of specific inflammatory pathways, including MAPK and transcription factors like STAT-3, is critical for ST7-mediated meningitis.
- Understanding these mechanisms provides insights into controlling S. suis ST7 infections.
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Bacterial Meningitis I: Introduction
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