title: Fibrinogen is a ligand for the Staphylococcus aureus microbial surface components recognizing adhesive matrix molecules (MSCRAMM) bone sialoprotein-binding protein (Bbp).
abstract: Microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are bacterial surface proteins mediating adherence of the microbes to components of the extracellular matrix of the host. On Staphylococci, the MSCRAMMs often have multiple ligands. Consequently, we hypothesized that the Staphylococcus aureus MSCRAMM bone sialoprotein-binding protein (Bbp) might recognize host molecules other than the identified bone protein. A ligand screen revealed that Bbp binds human fibrinogen (Fg) but not Fg from other mammals. We have characterized the interaction between Bbp and Fg. The binding site for Bbp was mapped to residues 561-575 in the Fg Aα chain using recombinant Fg chains and truncation mutants in Far Western blots and solid-phase binding assays. Surface plasmon resonance was used to determine the affinity of Bbp for Fg. The interaction of Bbp with Fg peptides corresponding to the mapped residues was further characterized using isothermal titration calorimetry. In addition, Bbp expressed on the surface of bacteria mediated adherence to immobilized Fg Aα. Also, Bbp interferes with thrombin-induced Fg coagulation. Together these data demonstrate that human Fg is a ligand for Bbp and that Bbp can manipulate the biology of the Fg ligand in the host.
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vazquez
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Horndahl
authors.forename: Vannakambadi K
authors.initials: VK
authors.lastname: Ganesh
authors.forename: Emanuel
authors.initials: E
authors.lastname: Smeds
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.forename: Magnus
authors.initials: M
authors.lastname: Hook
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010449:Peptide Mapping / Q000379:methods; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008024:Ligands; C509820:MSCRAMM proteins, Staphylococcus; D011994:Recombinant Proteins; C405490:bone sialoprotein-binding protein, Staphylococcus aureus; D005340:Fibrinogen