title: Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.
abstract: Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis.
authors.affiliation: Glycobiology Research and Training Center, Departments of Medicine and Cellular & Molecular Medicine, University of California, San Diego, San Diego, California, United States of America.
authors.forename: Lingquan
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Medicine, San Francisco Veterans Affairs Medical Center and the University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Bensing
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Supaporn
authors.initials: S
authors.lastname: Thamadilok
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, California, United States of America.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, California, United States of America.
authors.forename: Kam
authors.initials: K
authors.lastname: Lau
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, California, United States of America.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ruhl
authors.affiliation: Department of Medicine, San Francisco Veterans Affairs Medical Center and the University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sullam
authors.affiliation: Glycobiology Research and Training Center, Departments of Medicine and Cellular & Molecular Medicine, University of California, San Diego, San Diego, California, United States of America.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D004697:Endocarditis, Bacterial / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D040081:Protein Array Analysis; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism; D054773:Streptococcus gordonii / Q000378:metabolism* / Q000472:pathogenicity; D013298:Streptococcus sanguis / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D037521:Virulence Factors