The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Area of Science:

• Microbiology
• Infectious Diseases
• Neonatal Health

Background:

• Streptococcus agalactiae (group B Streptococcus; GBS) is a major cause of neonatal meningitis.
• A specific clone, GBS ST-17, is linked to a severe form of the disease, late-onset disease (LOD).
• The infection pathway for LOD is not fully understood, but an oral route is suspected.

Purpose of the Study:

• To identify novel virulence factors specific to the hypervirulent GBS ST-17 clone.
• To investigate the role of identified factors in GBS pathogenesis and neonatal meningitis.
• To explore potential therapeutic targets for GBS infections.

Main Methods:

• Identification and characterization of a novel ST-17-specific surface protein, HvgA.
• Assessment of bacterial adhesion to intestinal and blood-brain barrier cells in vitro.
• Evaluation of HvgA's role in colonization, translocation, and meningitis in a mouse model via oral inoculation.

Main Results:

• A novel ST-17-specific protein, hypervirulent GBS adhesin (HvgA), was identified.
• HvgA expression significantly enhanced GBS adhesion to intestinal and blood-brain barrier cells.
• HvgA was essential for oral GBS colonization, intestinal barrier crossing, and development of meningitis in mice.

Conclusions:

• HvgA is a critical virulence factor for GBS ST-17, enabling hypervirulence in the neonatal context.
• HvgA facilitates bacterial adherence and translocation across host barriers, leading to meningitis.
• HvgA represents a promising target for developing new diagnostic tools and antibacterial therapies against GBS.