Glycan-metabolizing enzymes in microbe-host interactions: the Streptococcus pneumoniae paradigm

Streptococcus pneumoniae is a frequent colonizer of the upper airways; however, it is also an accomplished pathogen capable of causing life-threatening diseases. To colonize and cause invasive disease, this bacterium relies on a complex array of factors to mediate the host-bacterium interaction. The respiratory tract is rich in functionally important glycoconjugates that display a vast range of glycans, and, thus, a key component of the pneumococcus-host interaction involves an arsenal of bacterial carbohydrate-active enzymes to depolymerize these glycans and carbohydrate transporters to import the products. Through the destruction of host glycans, the glycan-specific metabolic machinery deployed by S. pneumoniae plays a variety of roles in the host-pathogen interaction. Here, we review the processing and metabolism of the major host-derived glycans, including N- and O-linked glycans, Lewis and blood group antigens, proteoglycans, and glycogen, as well as some dietary glycans. We discuss the role of these metabolic pathways in the S. pneumoniae-host interaction, speculate on the potential of key enzymes within these pathways as therapeutic targets, and relate S. pneumoniae as a model system to glycan processing in other microbial pathogens.