Dr. Jennifer Kohler

Seminar Details

Host: Dr. Vlad Panin

Time: 4:00pm-5:00pm

Location: BICH 108

Seminar Abstract

Within the gastrointestinal tract, the epithelial surface is coated with a mucus layer that is a critical mediator of communication with the diverse community of microorganisms that form the gut microbiome.  The intestinal epithelial mucus layer is composed primarily of heavily O-glycosylated glycoproteins, called mucins, along with additional N-linked glycoproteins and glycolipids.  A defining characteristic of the mucus layer is the presence of the fucose monosaccharide.  Fucosylation of the intestinal epithelial occurs in a interleukin 22 (IL-22)-dependent manner in response to colonization with certain species of commensal bacteria, and fucose serves as nutrient for many gut microbes. However, pathogens also take advantage of intestinal fucosylation, and use recognition of fucosylated epitopes as a means to attack host cells.  I will discuss how cholera toxin exploits cell surface fucosylation to enter and intoxicate host cells.  While cholera toxin has long been known to bind to the glycolipid GM1 with high affinity, we found little GM1 in human intestinal epithelial cells. Rather, an important factor in binding of cholera toxin to human cells is recognition of fucosylated structures. In a colonic epithelial cell line, we find that cholera toxin recognizes both fucosylated glycoproteins and glycolipids. Knockout of B3GNT5, an enzyme required for synthesis of fucosylated glycosphingolipids (GSLs), reduces cholera toxin binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication. Knockout of B3GALT5, which results in increased production of fucosylated O-linked glycans, significantly increases cholera toxin binding and intoxication. These findings provide insight into the molecular determinants regulating sensitivity of host cells to cholera toxin