Serum opacity factor is a streptococcal receptor for the extracellular matrix protein fibulin-1.

The adhesion of bacteria to host tissues is often mediated by interactions with extracellular matrices. Herein, we report on the interactions of the group A streptococcus, Streptococcus pyogenes, with the extracellular matrix protein fibulin-1. S. pyogenes bound purified fibulin-1 in a dose-dependent manner. Genetic ablation of serum opacity factor (SOF), a virulence determinant of S. pyogenes, reduced binding by approximately 50%, and a recombinant peptide of SOF inhibited binding of fibulin-1 to streptococci by approximately 45%. Fibulin-1 bound to purified SOF2 in a dose-dependent manner with high affinity (K(d) = 1.6 nm). The fibulin-1-binding domain was localized to amino acid residues 457-806 of SOF2, whereas the fibronectin-binding domain is contained within residues 807-931 of SOF2, indicating that these two domains are separate and distinct. Fibulin-1 bound to recombinant SOF from M types 2, 4, 28, and 75 of S. pyogenes, indicating that the fibulin-1-binding domain is likely conserved among SOF from different serotypes. Mixed binding experiments suggested that gelatin, fibronectin, fibulin-1, and SOF form a quaternary molecular complex that enhanced the binding of fibulin-1. These data indicate that S. pyogenes can interact with fibulin-1 and that SOF is a major streptococcal receptor for fibulin-1 but not the only receptor. Such interactions with fibulin-1 may be involved in the adhesion of S. pyogenes to extracellular matrices of the host.