title: Bacterial fibronectin-binding proteins and endothelial cell surface fibronectin mediate adherence of Staphylococcus aureus to resting human endothelial cells.
abstract: Adhesion of Staphylococcus aureus to human endothelial cells is implicated in the pathogenesis of invasive staphylococcal disease. The adhesion to endothelial cells of isogenic mutants defective in defined surface structures was studied. Three strains of S. aureus defective in fibronectin-binding proteins FnBPA and FnBPB showed reduced adhesion. This was fully restored by complementation of a FnBPA- FnBPB- mutant derived from strain 8325-4 with a multicopy plasmid encoding FnBPA or FnBPB. Adhesion of mutants defective in other surface structures was unaffected. Anti-fibronectin antibodies blocked adhesion of 8325-4 to endothelial cells, while adhesion of strains 8325-4, P1 and five clinical isolates was inhibited by the recombinant form of the binding domain of FnBPB (rFNBD) from Streptococcus dysgalactiae. Adherence of bacterial aggregates resulting from the presence of purified fibrinogen was also inhibited by rFNBD protein. Three strains of S. aureus defective in FnBPA and FnBPB were not internalized by endothelial cells. S. aureus FnBPs mediate adhesion to human endothelial cells and are required for subsequent internalization, interactions of potential relevance to pathogenesis and treatment.
authors.affiliation: Interdepartmental Academic Unit of Microbiology and Infectious Diseases, Oxford University, Oxford, UK4.|Nuffield Department of Pathology and Bacteriology1, and Bone Infection Unit, Nuffield Orthopaedic Centre and Nuffield Department of Medicine3, The John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland2.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.affiliation: Nuffield Department of Pathology and Bacteriology1, and Bone Infection Unit, Nuffield Orthopaedic Centre and Nuffield Department of Medicine3, The John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cameron
authors.affiliation: Interdepartmental Academic Unit of Microbiology and Infectious Diseases, Oxford University, Oxford, UK4.|Nuffield Department of Pathology and Bacteriology1, and Bone Infection Unit, Nuffield Orthopaedic Centre and Nuffield Department of Medicine3, The John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Berendt
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004697:Endocarditis, Bacterial / Q000382:microbiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D000906:Antibodies; D001426:Bacterial Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D011994:Recombinant Proteins; C078635:fibronectin-binding proteins, bacterial; D005340:Fibrinogen