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.
Courtney
Harry S
HS
Veterans Affairs Medical Center, Memphis, TN 38163, USA. hcourtney@utmem.edu
Li
Yi
Y
Twal
Waleed O
WO
Argraves
W Scott
WS
D001426:Bacterial Proteins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011994:Recombinant Proteins; C060820:fibulin; C021908:opacity factor; D005780:Gelatin; D010447:Peptide Hydrolases