Acquisition of factor H by a novel surface protein on group B Streptococcus promotes complement degradation

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Pathogenic microbes utilize host complement regulators like factor H (FH) as a virulence mechanism to evade immune responses.
• Group B Streptococcus (GBS) type III is hypothesized to bind FH via capsular sialic acid, but this interaction and its mechanism remain unproven.

Purpose of the Study:

• To demonstrate and identify the mechanism of factor H (FH) binding to GBS type III.
• To elucidate how GBS type III utilizes FH to evade complement-mediated opsonization and host defense.

Main Methods:

• Incubation of wild-type and mutant GBS strains with human serum or purified FH.
• Assessment of complement component degradation (C3b, C5, C9) via functional assays.
• Protease treatment of GBS, overlay assays, mass spectrometry, and recombinant protein analysis to identify the FH receptor.

Main Results:

• Factor H (FH) bound to both wild-type and acapsular GBS strains.
• GBS-bound FH retained cofactor activity, leading to significant C3b degradation and reduced downstream complement activation.
• The streptococcal histidine triad (SHT) surface protein was identified as the direct receptor for FH on GBS type III.

Conclusions:

• The streptococcal histidine triad (SHT) protein is a novel factor H (FH)-binding protein on GBS type III.
• GBS type III employs SHT to bind FH, a mechanism that inhibits complement opsonization and promotes bacterial survival within the host.