Life-threatening complications from bacterial infections, such as sepsis and septic shock, are the second leading cause of death among patients in non-coronary intensive care units killing up to 146 000 patients each year in Europe. These alarming findings prompted many research groups, to search for novel strategies to treat severe infectious diseases. Many of these approaches are focused on so-called “host effector systems”, since evidence has accumulated that complications from an infection are caused by an over-stimulation of host defense systems that are modulated by bacteria or bacterial products. In severe infections, such as sepsis and septic shock, vascular leakage, increased cytokine levels, and coagulation/fibrinolysis dysfunction are often observed. Thus, the research projects presented in this application focus on the identification and characterization of molecular mechanisms that lead to these complications with a focus on severe infections caused by the human pathogen Streptococcus pyogenes. The results obtained from such investigations could be used for the discovery of novel treatments in infectious diseases.