Promotion of phagocytosis of Streptococcus pyogenes in human blood by a fibrinogen-binding peptide.

The binding of fibrinogen to M-related protein (Mrp) is known to contribute to the ability of Streptococcus pyogenes to evade phagocytosis by preventing the deposition of complement on the streptococcal surface. The objectives of this investigation were to map the common fibrinogen-binding domain of Mrp and to determine if this domain has a therapeutic potential to enhance phagocytosis of S. pyogenes in human blood. Using a series of recombinant, truncated proteins of Mrp, two fibrinogen-binding domains (FBD) were mapped. FBD1 was contained within amino acid residues 1-55 of Mrp and FBD2 within residues 81-138. FBD2 is found in all Mrp sequenced to date whereas FBD1 is not. Both FBD1 and FBD2 peptides but not a control peptide blocked the binding of fibrinogen to S. pyogenes and promoted phagocytosis of the streptococci in human blood. The data support the hypothesis that the binding of fibrinogen by S. pyogenes is centrally involved in their resistance to phagocytosis in human blood and suggest that treatments that interfere with the binding of fibrinogen to S. pyogenes may help in fighting infections by these organisms.