How does Streptococcus pyogenes hijack the plasminogen activation system for invasion?

Group A Streptococcus hijacks host plasminogen to facilitate colonization and dissemination. This infection can lead to life-threatening infections such as scarlet fever, septicemia, necrotizing fasciitis and streptococcal toxic shock syndrome, facilitated by bacterial plasminogen receptors and activators. This project will investigate the molecular and structural interactions between bacterial receptor/activator and plasminogen and the consequence of interfering with these interactions. We will use crystallography, cryo-electron microscopy and surface plasmon resonance to study the receptor protease interaction. We will prepare monoclonal antibodies to block the receptor/plasminogen interactions and any high-affinity antibodies generated in the studies will be tested for their therapeutic potentials in animal model studies.