Oral Presentation Lorne Infection and Immunity 2014

The Impact of Plasminogen Aquisition on the Early Immune Response to Group A Streptococcal Infection (#11)

Martina Sanderson-Smith 1
  1. University Of Wollongong, WOLLONGONG, NSW, Australia

Streptococcus pyogenes (group A streptococcus; GAS) is the major etiological agent of a variety of human infections, including the self-limiting infections pharyngitis and impetigo; and the invasive diseases necrotising fasciitis, bacteraemia and toxic shock syndrome. It is estimated that 700 million cases of localised GAS infection and 600,000 cases of invasive GAS infection occur each year worldwide. Approximately 25% of invasive infections are fatal1. A mounting body of clinical, epidemiological and experimental evidence suggests an important role for the host fibrinolytic system in GAS virulence3,2 .Experimental models of GAS infection suggest that GAS strains that can acquire cell surface plasmin are able to degrade fibrin clots that would normally block GAS dissemination. Furthermore, GAS interact with plasminogen in a highly species specific manner, whereby the secreted protein streptokinase (Ska) exclusively activates human plasminogen. The purpose of this study was to examine how unregulated host plasmin on the surface of GAS may endow it with the ability to evade the innate immune response. Using a humanised plasminogen mouse model of infection, and a series of isogenic bacterial mutants attenuated for the ability to interact with the plasminogen activation system, we show that plasminogen acquisition and activation contributes to multiple stages of GAS infection, and significantly influences the early immune response to GAS, thereby augmenting the virulence of this pathogen.

  1. Carapetis, J. R., Steer, A. C., Mulholland, E. K. and Weber, M. (2005). The global burden of group A streptococcal diseases. Lancet Infect Dis 5(11): 685-94.
  2. Sun, H., Ringdahl, U., Homeister, J. W., Fay, W. P., Engleberg, N. C., Yang, A. Y., Rozek, L. S., Wang, X., Sjobring, U. and Ginsburg, D. (2004). Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 305(5688): 1283-6.
  3. Sanderson-Smith, M. L., Dinkla, K, Cole, J.N, Cork, A.J, Maamary,P.G, McArthur, J.D, Chhatwal, G.S, and Walker, M.J (2008). M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate. Faseb J 22(8): 2715-22.