Group B Streptococcus transcriptome when interacting with brain endothelial cells

Area of Science:

• Microbiology
• Neuroscience
• Genetics

Background:

• Group B Streptococcus (GBS) is the primary cause of bacterial meningitis in newborns.
• GBS invades the central nervous system by crossing the blood-brain barrier (BBB) and meningeal-cerebrospinal fluid barrier (mBCSFB).
• Previous GBS virulence factor identification relied on genetic screening.

Purpose of the Study:

• To identify GBS virulence-associated genes using RNA-sequencing (RNA-seq) during interaction with brain endothelial cells (BECs).
• To investigate the role of downregulated genes, specifically codY, in GBS pathogenesis.
• To provide transcriptomic data and validated findings for future GBS-BBB interaction research.

Main Methods:

• RNA-sequencing (RNA-seq) of GBS co-cultured with induced pluripotent stem cell-derived BECs (iBECs).
• Quantitative PCR (qPCR) to validate RNA-seq findings for codY expression.
• Generation and phenotypic analysis of GBS codY mutants in two in vitro BEC models.

Main Results:

• Out of 2,068 GBS genes, 430 showed differential expression upon BEC interaction, with most (360) downregulated.
• The transcriptional repressor codY was significantly downregulated during GBS-BEC interaction.
• GBS mutants lacking codY exhibited increased adherence and invasion capabilities in BEC models.

Conclusions:

• RNA-seq is a valuable tool for identifying GBS virulence modulators during BEC interaction.
• Downregulation of codY is a key event in GBS pathogenesis, enhancing bacterial BBB traversal.
• This study provides a validated transcriptomic dataset offering insights into GBS-BBB interaction pathways.