Molecular Horizons Seminar - Dr Nichollas Scott

Protein glycosylation is an important but poorly understood aspect of microbial physiology. Over the last decade, significant strides have been made in characterizing bacterial glycosylation, with mass spectrometry (MS) emerging as an indispensable tool. While early studies focused on confirming the presence of glycosylation by repurposing eukaryotic glycoproteomic techniques, the unique characteristics of microbial glycosylation necessitate the development of fit-for-purpose microbial glycoproteomic approaches. Focusing on bacterial O-linked glycosylation our work seeks to improve our understanding of the substrates and functions of microbial glycosylation to enhance human health. By implementing tailored MS-based approaches, chemical labelling techniques, and antibody-based enrichment approaches targeting bacterial specific carbohydrates, we can now identify and track hundreds of glycoproteins across pathogenic species. Leveraging these new tools we have found that the glycans used for protein glycosylation appear extremely homogenous in most bacterial species. Probing the mechanism responsible for this glycan fidelity, we have discovered that blocking protein glycosylation glycan biosynthesis can result in dramatic impacts on bacterial viability. Collectively, this work demonstrates that by expanding the microbial glycoproteomics toolkit new insights into O-linked glycan biosynthesis pathways can be gained and that microbial glycosylation systems maybe ideal targets for developing antimicrobial therapies.