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. <i>Streptococcus oralis</i> is a leading cause of subacute infective endocarditis. Binding to platelets is a critical step in disease; however, the mechanisms utilized by <i>S. oralis</i> remain largely undefined. Studies revealed that <i>S. oralis</i>, like <i>Streptococcus gordonii</i> and <i>Streptococcus sanguinis</i>, binds platelets via terminal sialic acid. However, unlike those organisms, <i>S. oralis</i> produces a neuraminidase, NanA, which cleaves terminal sialic acid. Further studies revealed that following NanA-dependent removal of terminal sialic acid, <i>S. oralis</i> bound exposed β-1,4-linked galactose. Adherence to both these carbohydrates required Fap1, the <i>S. oralis</i> member 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.