Principal Investigator Laura Kiessling
While we need to fight off infections caused by bacteria, fungi, viruses, and other pathogens, we harbor a collection of these species as our microbiome. The glycans (polysaccharides, glycoproteins, glycolipids, etc) displayed on a cell surface vary with cell type and cell state. These differences in glycosylation serve as cellular identification codes. We are elucidating how families of carbohydrate-binding proteins, or lectins, read microbial IDs to influence our microbiota and protect our epithelial surfaces. Humans have about 50 soluble lectins, many of which are produced at sites vulnerable to microbial invasion. Understanding these protein-carbohydrate interactions at a molecular level will facilitate microbial identification and the development of new antibiotics and antimicrobial therapeutics.
One protein of interest is human intelectin-1 (hITLN-1), which we have shown does not bind human glycans; rather, this protein exclusively recognizes microbial glycans. This selectivity is intriguing because hITLN-1 (also called Omentin-1) is associated with diabetes, inflammatory bowel disease, asthma, and gastrointestinal cancers. We used
X-ray crystallography to determine the structure of hITLN-1-glycan complex. This structure unmasked the common recognition mode among the diverse ligands: a bound calcium ion coordinates a terminal exocyclic 1,2-diol on the glycan ligand. We postulate that the specificity of microbe-binding lectins could be harnessed to diagnose diseases of microbiome dysfunction, to promote the colonization of beneficial species (prebiotics, probiotics) or to eliminate unwanted species (antibiotics).