title: Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis.
abstract: Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified-a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (approximately 2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.
authors.affiliation: The Philips Institute of Oral and Craniofacial Molecular Biology, Richmond, VA 23298-0566, USA.
authors.forename: Lauren Senty
authors.initials: LS
authors.lastname: Turner
authors.forename: Taisei
authors.initials: T
authors.lastname: Kanamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Unoki
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Munro
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Todd
authors.initials: T
authors.lastname: Kitten
mesh_terms: D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004697:Endocarditis, Bacterial / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011817:Rabbits; D013290:Streptococcal Infections / Q000235:genetics / Q000378:metabolism*; D013298:Streptococcus sanguis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; C509821:sortase B; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases
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