A bacterial sulfoglycosidase highlights mucin O -glycan breakdown in the gut ecosystem

Mucinolytic bacteria modulate host–microbiota symbiosis and dysbiosis through their ability to degrade mucin O -glycans. However, how and to what extent bacterial enzymes are involved in the breakdown process remains poorly understood. Here we focus on a glycoside hydrolase family 20 sulfoglycosidase (BbhII) from Bifidobacterium bifidum , which releases N -acetylglucosamine-6-sulfate from sulfated mucins. Glycomic analysis showed that, in addition to sulfatases, sulfoglycosidases are involved in mucin O -glycan breakdown in vivo and that the released N -acetylglucosamine-6-sulfate potentially affects gut microbial metabolism, both of which were also supported by a metagenomic data mining analysis. Enzymatic and structural analysis of BbhII reveals the architecture underlying its specificity and the presence of a GlcNAc-6S-specific carbohydrate-binding module (CBM) 32 with a distinct sugar recognition mode that B. bifidum takes advantage of to degrade mucin O -glycans. Comparative analysis of the genomes of prominent mucinolytic bacteria also highlights a CBM-dependent O -glycan breakdown strategy used by B. bifidum .