Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells.
Several microbial pathogens have been reported to interact with glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix. Here we demonstrate that M protein, a major surface-expressed virulence factor of the human bacterial pathogen, Streptococcus pyogenes, mediates binding to various forms of GAGs. Hence, S. pyogenes strains expressing a large number of different types of M proteins bound to dermatan sulfate (DS), highly sulfated fractions of heparan sulfate (HS) and heparin, whereas strains deficient in M protein surface expression failed to interact with these GAGs. Soluble M protein bound DS directly and could also inhibit the interaction between DS and S. pyogenes. Experiments with M protein fragments and with streptococci expressing deletion constructs of M protein, showed that determinants located in the NH2-terminal part as well as in the C-repeat region of the streptococcal proteins are required for full binding to GAGs. Treatment with ABC-chondroitinase and HS lyase that specifically remove DS and HS chains from cell surfaces, resulted in significantly reduced adhesion of S. pyogenes bacteria to human epithelial cells and skin fibroblasts. Together with the finding that exogenous DS and HS could inhibit streptococcal adhesion, these data suggest that GAGs function as receptors in M protein-mediated adhesion of S. pyogenes.
Frick
Inga-Maria
IM
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Sweden. Inga-Maria.Frick@medkem.lu.se
Schmidtchen
Artur
A
Sjöbring
Ulf
U
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000166:cytology; D017353:Gene Deletion; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D013297:Streptococcus pyogenes / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D037521:Virulence Factors / Q000737:chemistry*
D001426:Bacterial Proteins; D006025:Glycosaminoglycans; D037521:Virulence Factors; D003871:Dermatan Sulfate