Degradation of mucin O-glycans by a human gut symbiont requires a complex enzyme repertoire and promotes colonization

Abstract

Secreted mucins are the major component of the mucus layer that protects intestinal epithelial surfaces by blocking excessive interactions with the microbiota. Mucins are complex glycoproteins decorated with over 100 different O-glycans. Some bacteria can utilize mucins and excessive degradation has been associated with disruption of the mucus barrier and inflammation. Despite the importance of mucins, a detailed enzymatic pathway by which gut bacteria degrade colonic mucin O-glycans and the impact of this process on gut colonization are unknown. Here, we identified >100 genes that are expressed by the symbiont Bacteroides thetaiotaomicron during growth on different O-glycan substrates, revealing effects of glycan structure on gene expression. The characterization of 33 glycoside hydrolase enzymes revealed the pathway for colonic O-glycan degradation by this bacterium. In vivo competition experiments show that multiple exo-acting enzymes targeting mucin capping structures are central to gut colonization and may provide targets to inhibit bacterial mucin degradation.