Binding of the Streptococcus gordonii Surface Glycoprotein Hsa to alpha(2-3) Linked Sialic Acid Residues on Fibronectin

ABSTRACT

The binding of microorganisms to platelets is a critical step in the development of infective endocarditis. In Streptococcus gordonii, this binding is mediated in part by serine-rich repeat proteins, which interact directly with sialic acid residues located on GPIIb receptors in the platelet membrane. In this study, we found that S. gordonii DL1 strain binds to platelets through bridging between sialic acid residue of fibronectin and serine-rich repeat protein (Hsa). Pretreatment of fibronectin with sialidases specific for alpha(2-3)-linked sialic acids was shown to significantly inhibit binding of the DL1 strain and the binding region(BR) of Hsa protein. Similarly, pre-incubation of bacteria or BR of Hsa with alpha(2-3)-sialyl-N-acetyllactosamine blocked fibronectin binding in the DL1 strain, but not the M99 strain. Together, these data show that the alpha(2-3)-sialic acid residues of fibronectin play an important role in the binding of S. gordonii DL1 to fibronectin through interactions with the Hsa receptor. This interaction is thought to play an important role in the development of pathogenic endocarditis, and may represent an important therapeutic target for the treatment of infective endocarditis.