Supplementary Material for: Streptococcus pyogenes Escapes Killing from Extracellular Histones through Plasminogen Binding and Activation by Streptokinase

<p>Histones are small basic proteins and highly conserved among eukaryotes. Their main function is binding, packaging and organizing of DNA in the nucleus, but extracellular histones are also potent antimicrobial proteins. Here we found that <i>Streptococcus pyogenes - </i>an important human pathogen - protects itself from histone-killing by the acquisition of plasminogen. Plasminogen, bound to the streptococcal surface, efficiently prevents histone-mediated killing. Moreover, the streptokinase/plasminogen complex degrades all classes of histones and abrogates their antibacterial and hemolytic effects. This novel streptokinase-mediated virulence mechanism may contribute to the escape of <i>S. pyogenes</i> from the human innate immune System.</p

Prothrombotic and Proinflammatory Activities of the beta-Hemolytic Group B Streptococcal Pigment

A prominent feature of severe streptococcal infections is the profound inflammatory response that contributes to systemic toxicity. In sepsis the dysregulated host response involves both immunological and nonimmunological pathways. Here, we report a fatal case of an immunocompetent healthy female presenting with toxic shock and purpura fulminans caused by group B streptococcus (GBS; serotype III, CC19). The strain (LUMC16) was pigmented and hyperhemolytic. Stimulation of human primary cells with hyperhemolytic LUMC16 and STSS/NF-HH strains and pigment toxin resulted in a release of proinflammatory mediators, including tumor necrosis factor, interleukin (IL)-1 beta, and IL-6. In addition, LUMC16 induced blood clotting and showed factor XII activity on its surface, which was linked to the presence of the pigment. The expression of pigment was not linked to a mutation within the CovR/S region. In conclusion, our study shows that the hemolytic lipid toxin contributes to the ability of GBS to cause systemic hyperinflammation and interferes with the coagulation system.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc