Two complementary α-fucosidases from promote complete degradation of host-derived carbohydrate antigens.

An important aspect of the interaction between the opportunistic bacterial pathogen and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including - and -linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of Although is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown. Here, we identified two pneumococcal enzymes, GH29 and GH95, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively. X-ray crystallography studies combined with functional assays revealed that GH29 is specific for the Lewis and Lewis antigen motifs and that GH95 is specific for the H(O)-antigen motif. Together, these enzymes could defucosylate Lewis and Lewis antigens in a complementary fashion. reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes. These experiments expand our understanding of the extensive capacity of to process host glycans and the likely roles of α-fucosidases in this. Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase GH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the -host interaction.