Arylsulfamates inhibit colonic Bacteroidota growth through a sulfatase-independent mechanism

Abstract

Excessive degradation of the colonic mucin layer by Bacteroides within the human gut microbiota drives inflammatory bowel disease (IBD) in mice. Bacterial carbohydrate sulfatases are key enzymes in gut colonization, and they are elevated in human IBD and correlate with disease severity. Selective inhibitors of carbohydrate sulfatases could function as sulfatase-selective drugs, allowing precise control of sulfatase activity while preserving these otherwise beneficial bacteria. Arylsulfamates are covalent inhibitors that target a catalytic formylglycine residue of steroid sulfatases, a residue that is also conserved in carbohydrate sulfatases. Here, we find that a library of aryl- and carbohy..