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Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host
Inga-Maria Frick1, Artur Schmidtchen, Ulf Sjöbring
1Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Sweden. Inga-Maria.Frick@medkem.lu.se
Abstract:
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.
Insights
Streptococcus pyogenes M protein binds to glycosaminoglycans (GAGs) like dermatan sulfate and heparan sulfate. This interaction is crucial for bacterial adhesion to human cells, suggesting GAGs act as key receptors.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Microbial pathogens often interact with host cell surface glycosaminoglycans (GAGs).
- M protein is a major surface virulence factor of Streptococcus pyogenes.
Purpose of the Study:
- To investigate the role of M protein in Streptococcus pyogenes adhesion to GAGs.
- To identify the mechanisms and binding sites involved in M protein-GAG interactions.
Main Methods:
- Bacterial strains expressing different M proteins were used to assess GAG binding.
- Experiments with soluble M protein fragments and deletion constructs identified binding regions.
- Enzymatic removal of GAGs (DS and HS) from cell surfaces was performed.
- Inhibition assays using exogenous GAGs were conducted.
Main Results:
- Streptococcus pyogenes strains expressing M protein bound to dermatan sulfate (DS), heparan sulfate (HS), and heparin.
- Soluble M protein directly bound DS and inhibited bacterial-GAG interactions.
- Specific regions in the NH2-terminal and C-repeat of M protein were essential for GAG binding.
- Removal of DS and HS significantly reduced bacterial adhesion to epithelial cells and fibroblasts.
Conclusions:
- GAGs, including DS and HS, serve as receptors for M protein-mediated adhesion of Streptococcus pyogenes.
- M protein's interaction with GAGs is a critical factor in S. pyogenes pathogenesis.
- Understanding this interaction can inform therapeutic strategies against S. pyogenes infections.