Sialidases and Fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria

The gut mucolytic specialist Akkermansia muciniphila is strongly associated with the integrity of the mucus layer. Mucin glycan utilization requires the removal of diverse protective caps, notably, fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those with double sulphated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the exclusive sialyl T-antigen specificity of a sialidase of a previously unknown family and catalytic apparatus. Key cell attached sialidases and fucosidases conferred mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, the sialic acid fucose did not contribute to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unique mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and the nutrient sharing between key mucus-associated bacteria.