Decoding the biosynthesis machinery and role in host-pathogen interactions of the streptococcal Group A Carbohydrate

Group A Streptococcus (StrepA) kills >500,000 people globally each year. New therapeutic options are urgently required. We will elucidate the mechanisms by which Group A Carbohydrate (GAC) is built into the bacterial cell wall and acts as a critical virulence factor in host-pathogen interactions. We will apply, and expand, our innovative techniques in carbohydrate biology to answer three major questions: - What are the molecular and structural details of the GAC biosynthesis machinery? - What is the role of GAC biosynthesis during cell division? - What is the role of GAC in host-pathogen interactions? We will provide detailed understanding of the GAC biosynthesis machinery on a mechanistic, structural, and cellular level by applying immunoprecipitation, proteomics, and structural studies. The role of GAC biosynthesis during cell division will be investigated using microscopy and genetics, coupled with biochemical approaches. Finally, we will define, the GAC-dependent mechanisms utilised by StrepA to colonise humans. We will identify molecular details of GAC?s role in host?pathogen interactions, the GAC-dependent immunological responses initiated and the resulting contributions of GAC to pathogenesis. We anticipate that our results will lead to the development of novel therapeutic approaches to combat StrepA and closely related pathogens and enable studies on other important bacterial carbohydrates.