Streptococcal fibronectin binding protein I (SfbI) mediates adherence to and invasion of Streptococcus pyogenes into human epithelial cells. In this study, we analysed the binding activity of distinct domains of SfbI protein towards its ligand, the extracellular matrix component fibronectin, as well as the biological implication of the binding events during the infection process. By using purified recombinant SfbI derivatives as well as in vivo expressed SfbI domains on the surface of heterologous organism Streptococcus gordonii, we were able to dissociate the two major streptococcal target domains on the human fibronectin molecule. The SfbI repeat region exclusively bound to the 30 kDa N-terminal fragment of fibronectin, whereas the SfbI spacer region exclusively bound to the 45 kDa collagen-binding fragment of fibronectin. In the case of native surface-expressed SfbI protein, an induced fit mode of bacteria-fibronectin interaction was identified. We demonstrate that binding of the 30 kDa fibronectin fragment to the repeat region of SfbI protein co-operatively activates the adjacent SfbI spacer domain to bind the 45 kDa fibronectin fragment. The biological consequence arising from this novel mode of fibronectin targeting was analysed in eukaryotic cell invasion assays. The repeat region of SfbI protein is mediating adherence and constitutes a prerequisite for subsequent invasion, whereas the SfbI spacer domain efficiently triggers the invasion process of streptococci into the eukaryotic cell. Thus, we were able to dissect bacterial adhesion from invasion by manipulating one protein. SfbI protein therefore represents a highly evolved prokaryotic molecule that exploits the host factor fibronectin not only for extracellular targeting but also for its subsequent activation that leads to efficient cellular invasion.
Talay, S., Zock, A., Rohde, M., Molinari, G., Oggioni, M.R., Pozzi, G., et al. (2000). Cooperative binding of human fibronectin to SfbI protein triggers streptococcal invasion into respiratory epithelial cells. CELLULAR MICROBIOLOGY, 2(6), 521-535 [10.1046/j.1462-5822.2000.00076.x].
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|Titolo:||Cooperative binding of human fibronectin to SfbI protein triggers streptococcal invasion into respiratory epithelial cells|
|Citazione:||Talay, S., Zock, A., Rohde, M., Molinari, G., Oggioni, M.R., Pozzi, G., et al. (2000). Cooperative binding of human fibronectin to SfbI protein triggers streptococcal invasion into respiratory epithelial cells. CELLULAR MICROBIOLOGY, 2(6), 521-535 [10.1046/j.1462-5822.2000.00076.x].|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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