title: Streptococcus oralis Neuraminidase Modulates Adherence to Multiple Carbohydrates on Platelets.
abstract: Adherence to host surfaces is often mediated by bacterial binding to surface carbohydrates. Although it is widely appreciated that some bacterial species express glycosidases, previous studies have not considered whether bacteria bind to multiple carbohydrates within host glycans as they are modified by bacterial glycosidases.Streptococcus oralisis a leading cause of subacute infective endocarditis. Binding to platelets is a critical step in disease; however, the mechanisms utilized byS. oralisremain largely undefined. Studies revealed thatS. oralis, likeStreptococcus gordoniiandStreptococcus sanguinis, binds platelets via terminal sialic acid. However, unlike those organisms,S. oralisproduces a neuraminidase, NanA, which cleaves terminal sialic acid. Further studies revealed that following NanA-dependent removal of terminal sialic acid,S. oralisbound exposed β-1,4-linked galactose. Adherence to both these carbohydrates required Fap1, theS. oralismember of the serine-rich repeat protein (SRRP) family of adhesins. Mutation of a conserved residue required for sialic acid binding by other SRRPs significantly reduced platelet binding, supporting the hypothesis that Fap1 binds this carbohydrate. The mechanism by which Fap1 contributes to β-1,4-linked galactose binding remains to be defined; however, binding may occur via additional domains of unknown function within the nonrepeat region, one of which shares some similarity with a carbohydrate binding module. This study is the first demonstration that an SRRP is required to bind β-1,4-linked galactose and the first time that one of these adhesins has been shown to be required for binding of multiple glycan receptors.
authors.affiliation: Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Anirudh K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Shireen A
authors.initials: SA
authors.lastname: Woodiga
authors.affiliation: Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Grau
authors.affiliation: Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, Ohio, USA Samantha.King@NationwideChildrens.org.|Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Samantha J
authors.identifier: http://orcid.org/0000-0003-2213-5822
authors.initials: SJ
authors.lastname: King
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism* / Q000382:microbiology*; D005690:Galactose / Q000378:metabolism; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D019533:Streptococcus oralis / Q000201:enzymology / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D005690:Galactose
keywords: Streptococcus oralis; adherence; endocarditis; host glycans; neuraminidase; platelets; serine-rich repeat protein; sialic acid; β-1,4-linked galactose