Grant: Banting Postdoctoral Fellowship Program

The human gut plays host to an incredibly complex microbial community. Beneficial gut microbes are shown alleviate inflammatory bowel and metabolic disease symptoms and protect against gut infections. The ability to degrade and utilize carbohydrates is essential to survival in the human gut and is reflected in the over representation of carbohydrate active enzymes and glycan binding proteins expressed by gut bacteria. Gut microbes utilize dietary glycans, primarily from plant sources. A prominent genus in the human gut microbiota, Bacteroides, possess well developed glycan utilization systems. Astoundingly, the Bacteroides ovatus genome encodes over 100 individual polysaccharide utilization loci (PULs). PULs are equipped with integral outer-membrane SusC-like TonB-dependent Transporters (TBDTs) paired with an outer-membrane lipid anchored glycan binding protein, SusD-homologue. Alongside the TBDTs are carbohydrate active enzymes in the periplasm or on the cell surface. Given the ubiquity of this class of TBDT in Bacteroides PULs and the great strides made recently in our understanding of glycan binding and degradation by gut microbes astonishingly little is known about this class of transporter. TBDTs are essential to Bacteroides glycan utilization in the gut and by extension, human health. In this research proposal I outline methodology to structurally and functionally characterize TBDTs targeting xyloglucan, ubiquitous a dietary glycan. I will explore cross-feeding, where keystone species like Bacteroides increase accessibility to complex glycans for other microbes, which can increase species diversity in the human gut. I will use in vivo growth studies to understand how glycan transport during utilization impact carbohydrate cross-feeding. A greater understanding of Bacteroides TBDTs and how they impact other gut bacteria will inform prebiotic strategies for use in inflammatory bowel diseases and the maintenance of a healthy gut flora.