| The overall aim of this project is to investigate the interactions of TAFI and B2GPI with S. pyogenes and the functional consequences thereof. We have established that TAFI binds to streptococcal proteins SclA and/or B, and B2GPI binds to protein H. Furthermore, we have established that peptides from B2GPI display antimicrobial actions. In order to reach our goals we propose to: 1. Clone and express the streptococcal binding proteins (SclA/B and protein H), and characterize the interaction. Also, streptococcal mutants that lack TAFI or B2GPI binding capacity will be generated.2. Identify target proteins that are (in)activated/modulated by streptococcal-bound TAFI and B2GPI.3. Identify mechanisms that trigger the formation of antibacterial peptides from B2GPI. The antibacterial effect will be tested on other bacterial species and in infectious animal models.4. Further establishment of a role for B2GPI as an anti-endotoxin scavenger5. Determine the role of S. pyogenes in the induction of antiphospholipid antibody generation. |
