Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Group B Streptococcus (GBS) is a significant human pathogen.
• The CsrRS (CovRS) two-component system regulates GBS virulence factors.

Purpose of the Study:

• To investigate the global gene expression regulated by the CsrRS system in GBS.
• To understand the conserved and strain-specific aspects of CsrRS regulon.
• To correlate CsrRS regulation with GBS virulence in different strains.

Main Methods:

• Global gene expression studies using RNA sequencing in GBS strains and their isogenic csrR and csrS mutants.
• In vitro phosphorylation-dependent DNA binding assays of CsrR.
• Murine models of systemic infection and septic arthritis to assess virulence.

Main Results:

• A conserved 39-gene CsrRS regulon was identified across different GBS strains.
• CsrR directly binds to promoter regions, mediating both gene activation and repression.
• Distinct gene regulation patterns and virulence hierarchies were observed between GBS strains 2603V/R and 515 mutants.
• Variability in CsrRS regulon and CsrS signaling effects on CsrR function was noted.

Conclusions:

• CsrRS regulates a core set of GBS virulence genes, with significant strain-specific variations.
• This variability in gene regulation and signaling likely contributes to GBS strain adaptation and pathogenesis.
• Understanding CsrRS variability is crucial for comprehending GBS host adaptation and disease potential.