Pathogen-host interactions at the surface of Streptococcus pyogenes

Sammanfattning: The bacterial surface can be thought of as the interface where pathogenic bacteria encounter the human host. Interactions between bacterial surface proteins and human proteins are important determinants of the eventual outcome of infection. A bacterial protein, Protein F1, that binds the human plasma and connective tissue protein fibronectin, was found to reduce the virulence of Streptococcus pyogenes in a mouse model of infection. Experiments with mice lacking plasma fibronectin indicate that interactions of Protein F1 with both plasma and cellular fibronectin reduce bacterial virulence. S. pyogenes secretes a cysteine proteinase, SpeB, that was found to reduce bacterial fibronectin-binding by degrading Protein F1 at the bacterial surface. Proteolytic reduction of fibronectin-binding resulted in reduced S. pyogenes adhesion and internalisation. Protein F1 was more sensitive to SpeB than M1 protein, and not protected from SpeB when in complex with fibronectin. SpeB can degrade the antimicrobial peptide LL-37. It was shown that SpeB in complex with the human proteinase inhibitor ?2-macroglobulin could still degrade LL-37. ?2-macroglobulin-SpeB complexes bound to the surface of S. pyogenes via the bacterial surface protein GRAB protected the bacterium from killing by LL-37. C3a, generated in the activation of the complement system, was shown to have antibacterial activity and a C3a-derived peptide protected mice against S. pyogenes infection.