Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus

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ABSTRACT Project 2: University of Delaware - Grimes The P01 entitled Multidimensional development of high-affinity anti-glycan antibodies to fight deadly bacterial infections aims to develop novel strategies to combat bacterial infections. The whole project grant aims to develop therapeutic antibodies for the treatment of bacterial resistant infections. Project 2, entitled “Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus” will focus on bacterial pathogen Staphylococcus aureus. S. aureus is typically treated with penicillin or glycopeptides; however precedent resistant stains to both classes of antibiotics have emerged. As such, the World Health Organization has placed it on the priority list for new antibiotics. Project 2 will focus on the synthesis of bacterial peptidoglycan (PGN) fragments from Staphylococcus aureus, with a strong emphasis on two modifications used by Sa to modify PGN: acetylation and wall teichoic acids (WTA). As the bacterial cell wall and peptidoglycans are critical to human health it represents an excellent antibody target: humans do not have these cell walls and they are essential to bacteria. The modified peptidoglycan fragments from S. aureus synthesized in the project will provide the biologically relevant fragments necessary to produce, characterize and validate the clinically relevant antibodies throughout this entire project.