Two complementary α-fucosidases from Streptococcus pneumonia promote complete degradation of host-derived carbohydrate antigens
Date
2019
Authors
Hobbs, Joanne K.
Pluvinage, Benjamin
Robb, Melissa
Smith, Steven P.
Boraston, Alisdair B.
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Biological Chemistry
Abstract
An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae. Although S. pneumoniae 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, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively. X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif. Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion. In vitro 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 S. pneumoniae 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 SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae–host interaction.
Description
Keywords
Streptococcus, glycoside hydrolase, host-pathogen interaction, structure-function, X-ray crystallography
Citation
Hobbs, J. K., Pluvinage, B., Robb, M., Smith, S. P., & Boraston, A. B. (2019). Two complementary α-fucosidases from Streptococcus pneumonia promote complete degradation of host-derived carbohydrate antigens. Journal of Biological Chemistry, 294(34), 12670-12682. https://doi.org/10.1074/jbc.RA119.009368.