How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

Significance The major nutrients available to the human microbiota are complex carbohydrates. Host glycans are important to this microbial community, particularly when dietary carbohydrates are scarce. The host glycans heparin and heparan sulfate are high-priority carbohydrates for Bacteroides thetaiotaomicron , a member of the human microbiota. The degradation of these complex carbohydrates is challenging, reflecting their highly variable sulfation patterns. How bacteria have adapted to depolymerize the myriad of substructures of this important class of glycosaminoglycan is unknown. Here, we show how enzyme consortia, displaying complementary functions, target the different features of these host glycans. Structural data reveal that the acidic groups of the glycans are key specificity determinants for enzymes and binding proteins that make up the degradative apparatus.