Most proteins in our immune system are glycoproteins where carbohydrates (glycans) influence function. Antibodies are central to our acquired immune system and glycans are very important for their proper interaction with white blood cells. Not surprisingly, bacteria have evolved enzymes (glycosidases) that destroy or alter these glycans. We have discovered the first enzyme, EndoS from Group A Streptococcus (GAS), which very specifically removes the glycans on IgG antibodies. GAS only infects humans and causes mild infections like strep throat and swine pox, but also serious life-threatening infections. The role of bacterial endoglycosidases in the infection process is currently unknown. In this project, we want to try to answer this question. We have access to a very sensitive and accurate mass spectrometric method where we can study the glycosylation of antibodies directly in samples from blood, throat and infected tissue. Preliminary experiments show that antibodies lose their glycan both locally in tonsillitis and in the blood in severe disseminated infection (sepsis). We will also examine antibody glycosylation in mice infected with the original bacterium and those lacking EndoS or similar enzymes. The results from our studies are important for understanding the basic mechanisms of how bacteria evade our immune system, but also open up new ways to diagnose and treat severe infectious disease.