The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome

Area of Science:

• Microbiology
• Pathogenesis
• Bacterial Virulence Factors

Background:

• Group B Streptococcus (GBS) causes neonatal sepsis and meningitis, with rising adult disease burden.
• Current intrapartum prophylaxis reduces mother-to-newborn GBS transmission but highlights the need for alternative anti-virulence strategies.
• Understanding GBS pathogenesis is key to developing novel therapies with reduced antibiotic exposure.

Purpose of the Study:

• To identify and characterize GBS homologs of the group A Streptococcus S protein.
• To evaluate the role of the GBS S protein in bacterial pathogenesis and virulence.
• To explore the GBS S protein as a potential target for anti-virulence therapies.

Main Methods:

• Construction and characterization of a GBS S protein deletion mutant (Δess).
• Quantitative proteome analysis of cell-surface epitopes.
• Assessment of bacterial virulence in a murine model of systemic infection.

Main Results:

• The GBS Δess mutant exhibited altered cell-surface properties, including defective polysaccharide retention.
• Proteome analysis revealed a dysregulated cell surface virulome in the Δess mutant.
• The Δess mutant displayed significantly attenuated virulence in a murine infection model.

Conclusions:

• The GBS S protein is a novel virulence determinant involved in maintaining cell-surface integrity and pathogen burden.
• Targeting the GBS S protein represents a promising strategy for developing new anti-virulence therapies.
• This study expands knowledge of streptococcal pathogenesis and identifies a potential therapeutic target for GBS infections.