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Fibronectin-binding protein B variation in Staphylococcus aureus.

Fiona M Burke1, Niamh McCormack, Simonetta Rindi

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Staphylococcus aureus fibronectin binding proteins B (FnBPB) show significant variation in human and bovine strains, leading to distinct antigenic properties while maintaining essential ligand-binding functions. This diversity may help the bacteria evade immune responses.

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Area of Science:

  • Microbiology
  • Immunology
  • Structural Biology

Background:

  • Fibronectin binding proteins A and B (FnBPA and FnBPB) are crucial for Staphylococcus aureus adhesion to host proteins like fibrinogen, elastin, and fibronectin.
  • Previous studies identified seven FnBPA isotypes based on variations in ligand-binding A domains, affecting antigenicity but not function.
  • This study investigates the variation within FnBPB in human and bovine S. aureus isolates, comparing it with FnBPA diversity.

Purpose of the Study:

  • To characterize the allelic variants and isotypes of FnBPB in S. aureus.
  • To compare the variation of FnBPB with that of FnBPA.
  • To assess the functional and antigenic implications of FnBPB diversity.

Main Methods:

  • Phylogenetic analysis of fnbB alleles.
  • Amino acid sequence comparison of FnBPB A domain isotypes.
  • Three-dimensional modeling to predict surface-exposed residues.
  • ELISA and surface plasmon resonance assays to evaluate ligand binding affinities.
  • Antigenic characterization using polyclonal and monoclonal antibodies.

Main Results:

  • Seven distinct fnbB allelic variants and corresponding FnBPB A domain isotypes were identified, showing 61-85% amino acid identity.
  • Phylogenetic analysis revealed inconsistencies between fnbB and fnbA gene evolution.
  • Variant residues are predicted to be surface-exposed, contributing to antigenic diversity.
  • All seven FnBPB isotypes demonstrated dose-dependent, saturable binding to fibrinogen, elastin, and fibronectin with similar affinities.
  • FnBPB binding to fibronectin was observed despite the absence of known fibronectin-binding motifs in the A domain.

Conclusions:

  • Seven FnBPB A domain isotypes exhibit distinct antigenic profiles while retaining conserved ligand-binding capabilities.
  • Variation in FnBPA and FnBPB across human and bovine S. aureus strains likely serves as an immune evasion strategy.
  • The novel mechanism of fibronectin binding by FnBPB A domains has implications for vaccine and immunotherapeutic development targeting S. aureus.