Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae.
Streptococcus pneumoniae produces three surface-associated exoglycosidases; a neuraminidase, NanA, a beta-galactosidase, BgaA, and a beta-N-acetylglucosaminidase, StrH. the proposed functions of NanA, which removes terminal sialic acid, include revealing receptors for adherence, affecting the function of glycosylated host clearance molecules, modifying the surface of other bacteria coinhabiting the same niche, and providing a nutrient source. However, it is unclear whether following desialylation S. pneumoniae can further deglycosylate human targets through the activity of BgaA or StrH. We demonstrate that NanA, BgaA and StrH act sequentially to remove sialic acid, galactose and N-acetylglucosamine and expose mannose on human glycoproteins that bind to the pneumococcus and protect the airway. In addition, both BgaA and NanA were shown to contribute to the adherence of unencapsulated pneumococci, to human epithelial cells. Despite these findings, triple exoglycosidase mutants colonized mice as well as their parental strains, suggesting that any effect of these genes on colonization and disease may be host species-specific. These studies highlight the importance of considering the complete ability of S. pneumoniae to deglycosylate human targets and suggest that in addition to NanA, BgaA and StrH also contribute to pneumococcal colonization and/or pathogenesis.
King
Samantha J
SJ
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. KingS@pediatrics.ohio-state.edu
Hippe
Karen R
KR
Weiser
Jeffrey N
JN
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D006001:Glycoconjugates / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000472:pathogenicity
D001426:Bacterial Proteins; D006001:Glycoconjugates; D006026:Glycoside Hydrolases; D008358:Mannose