Grant: Operating Grant

Understanding the structure and function of proteins has served to illuminate their critical functions in diverse organisms. Here we focus on a family of related enzymes from the Streptococcus pneumonia (the pneumococcus), which is a bacterium that often lives in the nose and throats of humans. This microorganism is an accomplished disease-causing germ that can cause mild ailments, such as earaches, to lethal illnesses like pneumonia, blood poisoning, and infections of the brain and central nervous system. Current vaccines and medicines (antibiotics) for treating pneumococcus infections are not always effective since this germ is constantly adapting to avoid both of these medical interventions. The importance of S. pneumoniae as a major disease-causing germ dictates intense research efforts be directed to understand how it causes infections with the aim of using this knowledge to guide eventual new treatment strategies. The human body has large amounts of carbohydrates with complex structures, termed glycans, displayed on the surface of cells and coating the surfaces of tissues (e.g. mucous). Remarkably, the pneumococcus relies on its ability to attack these glycans to colonize humans and ultimately cause disease. Our research is aimed at determining how this happens, at the molecular level. What glycans does the germ attack? What pneumococcal factors do this? What do these pneumococcal factors look like? What are the consequences of destroying certain host sugars? What effect do molecules that block these factors have on pneumococcal attack of host glycans. The results of this research will yield important research tools for the community but also such molecules are proving useful provide fundamewntal knowledge that could be used by other to develop new treatments to combat S. pneumoniae infections.