title: Growth of Streptococcus pneumoniae on human glycoconjugates is dependent upon the sequential activity of bacterial exoglycosidases.
abstract: In the human host, Streptococcus pneumoniae encounters a variety of glycoconjugates, including mucin, host defense molecules, and glycans associated with the epithelial surface. S. pneumoniae is known to encode a number of glycosidases that may modify these glycoconjugates in vivo. Three exoglycosidases, a neuraminidase (NanA), beta-galactosidase (BgaA), and N-acetylglucosaminidase (StrH), have been previously demonstrated to sequentially deglycosylate N-linked glycans on host defense molecules, which coat the pneumococcal surface in vivo. This cleavage is proposed to alter the clearance function of these molecules, allowing pneumococci to persist in the airway. However, we propose that the exoglycosidase-dependent liberation of monosaccharides from these glycoconjugates in close proximity to the pneumococcal surface provides S. pneumoniae with a convenient source of fermentable carbohydrate in vivo. In this study, we demonstrate that S. pneumoniae is able to utilize complex N-linked human glycoconjugates as a sole source of carbon to sustain growth and that efficient growth is dependent upon the sequential deglycosylation of the glycoconjugate substrate by pneumococcal exoglycosidases. In addition to demonstrating a role for NanA, BgaA, and StrH, we have identified a function for the second pneumococcal neuraminidase, NanB, in the deglycosylation of host glycoconjugates and have demonstrated that NanB activity can partially compensate for the loss or dysfunction of NanA. To date, all known functions of pneumococcal neuraminidase have been attributed to NanA. Thus, this study describes the first proposed role for NanB by which it may contribute to S. pneumoniae colonization and pathogenesis.
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43205-2696, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Burnaugh
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Frantz
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: King
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016296:Mutagenesis; D009439:Neuraminidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006001:Glycoconjugates; D011994:Recombinant Proteins; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D001616:beta-Galactosidase; D000118:Acetylglucosaminidase