DCAF15-mediated EphA2 degradation triggers disruption of the blood-brain barrier during Streptococcus suis meningitis
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Rendong Fang
PROVIDER: PXD070204 | iProX | Fri Oct 31 00:00:00 GMT 2025
REPOSITORIES: iProX
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Project description:Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. In this study,we evaluated the genetic difference of 40 Streptococcus suis strains belonging to various sequence types by comparative genomic hybridization to identify genes associated with the variation in pathogenicity using NimbleGen’s tilling microarray platform. Application of Comparative Phylogenomics to Identify Genetic Differences Relating to Pathogenicity of Streptococcus suis
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Project description:The interactions of Streptocococcus suis (S.suis) with human microvascular endothelial cells (hBMEC) are important process for S.suis passage across human blood brain barrier (BBB). S.suis has evolved precise mechanisms to alter gene expression depending on the distinct challenges posed by particular disease sites. Herein, a whole-genome DNA microarray was used to investigate the change of gene expression profile of S.suis after contact with hBMEC 3 h. comparison of RNA isolated from hBMEC-associated S.suis with RNA derived from control bacteria revealed significant differential changes for 175 S.suis genes including 123 up-regulated genes and 52 down-regulated genes at 3 h post infection. A cDNA microarray imprinted with 2156 genes representing about 98% of Streptococcus suis serotype 2 genome was used for transcriptome analysis . For two-sample (reference vs. test) microarray hybridization, Two-condition experiment, control vs contact with hBMEC 3 h, four replicates (two biological replicates, two technical replicates) at each condition.
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Project description:The interactions of Streptocococcus suis (S.suis) with human microvascular endothelial cells (hBMEC) are important process for S.suis passage across human blood brain barrier (BBB). S.suis has evolved precise mechanisms to alter gene expression depending on the distinct challenges posed by particular disease sites. Herein, a whole-genome DNA microarray was used to investigate the change of gene expression profile of S.suis after contact with hBMEC 1 h. comparison of RNA isolated from hBMEC-associated S.suis with RNA derived from control bacteria revealed significant differential changes for 219 S.suis genes including 131 up-regulated genes and 88 down-regulated genes at 1 h post infection. A cDNA microarray imprinted with 2156 genes representing about 98% of Streptococcus suis serotype 2 genome was used for transcriptome analysis . For two-sample (reference vs. test) microarray hybridization, Two-condition experiment, control vs contact with hBMEC 1 h, four replicates (two biological replicates, two technical replicates) at each condition.
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Project description:Streptococcus suis is a zoonotic pathogen that can invade the central nervous system (CNS) and cause meningitis in pigs and humans. The vascularized choroid plexus (ChP) epithelium, known as the blood-cerebrospinal fluid barrier (BCSFB), serves as a route for S. suis invasion of the CNS. In this study, we aimed to use human induced pluripotent stem cells (iPSC)-derived ChP organoids as an in vitro model to investigate S. suis interaction and infection at the BCSFB and the responses of ChP organoids to S. suis using transcriptomics. We also investigated whether the known plasminogen (Plg) binding to S. suis surface enolase and its conversion to proteolytic plasmin (Pln) would facilitate S. suis translocation across the ChP organoid epithelium and alter the ChP response to infection.
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Project description:The interactions of Streptocococcus suis (S.suis) with human microvascular endothelial cells (hBMEC) are important process for S.suis passage across human blood brain barrier (BBB). S.suis has evolved precise mechanisms to alter gene expression depending on the distinct challenges posed by particular disease sites. Herein, a whole-genome DNA microarray was used to investigate the change of gene expression profile of S.suis after contact with hBMEC 1 h. comparison of RNA isolated from hBMEC-associated S.suis with RNA derived from control bacteria revealed significant differential changes for 219 S.suis genes including 131 up-regulated genes and 88 down-regulated genes at 1 h post infection.
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Project description:The interactions of Streptocococcus suis (S.suis) with human microvascular endothelial cells (hBMEC) are important process for S.suis passage across human blood brain barrier (BBB). S.suis has evolved precise mechanisms to alter gene expression depending on the distinct challenges posed by particular disease sites. Herein, a whole-genome DNA microarray was used to investigate the change of gene expression profile of S.suis after contact with hBMEC 3 h. comparison of RNA isolated from hBMEC-associated S.suis with RNA derived from control bacteria revealed significant differential changes for 175 S.suis genes including 123 up-regulated genes and 52 down-regulated genes at 3 h post infection.
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Project description:Streptococcus suis is a major pig pathogen as well as an emerging zoonotic pathogen. Previous work has demonstrated that the S. suis extracellular amylopullulanase enzyme (ApuA) that degrades {alpha}-glucans also functions as an adhesin for porcine epithelial cells. To identify the mechanisms linking carbohydrate metabolism and virulence, we first compared the transcriptome of S. suis in minimal medium supplemented with glucose to minimal medium containing a complex carbohydrate pullulan as a carbon source. The relative expression of eighteen virulence genes including suilysin and apuA was increased during growth in presence of pullulan, compared to growth in glucose. Increased virulence potential of S. suis grown in pullulan was demonstrated using hemolytic assays and increased adhesion and invasion of porcine epithelial cells in vitro. A metabolic map of S. suis was generated and combined with transcriptome data to visualize the metabolic adaption of S. suis during adhesion and invasion of the porcine epithelial cells representing an in vitro model of infection. The role of carbon catabolite control in virulence gene regulation was investigated and the molecular mechanism of transcriptional regulation was elucidated for apuA. We demonstrate that relief of CcpA repression is a crucial transcriptional control mechanism linking carbohydrate mechanism and virulence. The model for the transcriptional regulation of two important virulence factors apuA and suilysin was verified by qPCR analysis of gene expression in S. suis recovered from the organs and blood of infected pigs.
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Project description:Identification of Genes and Genomic Islands Correlated with High Pathogenicity through Tilling Microarray-Based Comparative Genomics in S. suis. Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. S. suis isolates have been categorized into groups of different levels of pathogenicity, with sequence type (ST) ST1 clonal complex strains having a higher degree of virulence than other STs. However, the genetic basis of the differences in pathogenicity is still poorly understood. In this study, a comprehensive genomic comparison of 31 S. suis strains from different clinical sources with the genome sequence of the high pathogenicity (HP) strain GZ1 was conducted using NimbleGenM-bM-^@M-^Ys tilling microarray platform. Comparative genomic analysis on the 31 S. suis strains of different serotypes and ST types through tilling arrays.
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