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The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and

Clayton C Caswell1, Runlin Han, Kelley M Hovis

  • 1Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.

Molecular Microbiology
|December 21, 2007
PubMed

Insights

Streptococcus bacteria use collagen-like protein Scl1 to bind factor H (FH), a human immune regulator. This interaction helps bacteria evade immune responses like complement-mediated phagocytosis.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • The complement system is crucial for innate immunity, regulated by factor H (FH).
  • Pathogenic bacteria, like Group A Streptococcus (GAS), can evade complement attack by binding host FH.
  • Streptococcal collagen-like proteins (Scl) are implicated in host-pathogen interactions.

Purpose of the Study:

  • To investigate the interaction between M6-type GAS Scl1.6 protein and human factor H (FH).
  • To determine the functional significance of this Scl1.6-FH interaction in bacterial immune evasion.

Main Methods:

  • Affinity chromatography using recombinant Scl1.6 to isolate interacting proteins.
  • Mass spectrometry and Western immunoblotting to identify bound proteins.
  • Structure-function studies to map binding domains.
  • Functional assays to assess complement regulatory activity.

Main Results:

  • Scl1.6 specifically binds human factor H (FH) and FH-related proteins.
  • The globular domain of Scl1.6 mediates FH binding.
  • Phylogenetically related Scl1.55 also binds FH.
  • FH bound to Scl1.6 retains cofactor activity for C3b cleavage, inhibiting complement activation.
  • FH binds to Scl1.6 on the cell wall of M6-type GAS.

Conclusions:

  • A functional interaction between streptococcal Scl1 and human FH has been identified.
  • This interaction likely contributes to GAS evasion of complement-mediated opsonization and phagocytosis.
  • Targeting this interaction could be a strategy to enhance GAS clearance.

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