A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Group B Streptococcus (GBS) causes severe infections in newborns and adults.
• Pili, filamentous appendages on GBS surface, have been recently identified.
• The role of GBS pili in disease pathogenesis remains largely unknown.

Purpose of the Study:

• To investigate the functional role of PilB, the main protein subunit of GBS pili, in bacterial virulence.
• To analyze an isogenic GBS pilB knockout strain and study heterologous pilB gene expression in Lactococcus lactis.

Main Methods:

• Created a GBS pilB knockout strain to assess its susceptibility to immune cell killing.
• Investigated GBS resistance to cathelicidin antimicrobial peptides.
• Evaluated GBS virulence in vivo using a mouse model.
• Overexpressed the pilB gene in Lactococcus lactis to assess its impact on virulence and host defenses.

Main Results:

• GBS lacking PilB showed increased susceptibility to killing by macrophages and neutrophils.
• PilB mediates resistance to cathelicidin antimicrobial peptides.
• PilB-deficient GBS mutants exhibited reduced virulence and faster clearance from the bloodstream in mice.
• Overexpression of pilB in Lactococcus lactis conferred enhanced resistance to phagocytosis, increased bloodstream survival, and induced virulence in a mouse model.

Conclusions:

• The GBS pilus backbone subunit, PilB, is essential for bacterial virulence.
• Gram-positive pili play a novel role in evading innate immune defenses, specifically phagocyte killing.
• PilB is a potential target for therapeutic interventions against GBS infections.