The ability of this protein to bind fibronectin was later confirmed [11]. In the same study, the revised A domain of FnBPA spanning residues 194-511 (Figure 1) was shown bind fibrinogen and elastin but not fibronectin. The minimum region of the FnBPA A domain needed for binding to fibrinogen and elastin is subdomains N23 (residues 194-511). The N1 sub-domain is not required for ligand www.selleckchem.com/products/thz1.html binding [11]. The

binding of FnBPs to fibronectin promotes the internalization of S. aureus into epithelial and endothelial cells which are not normally phagocytic [17, 18]. FnBP-mediated invasion occurs through the formation of a fibronectin bridge between S. aureus and the α5β1 integrin [18]. This may promote bacterial dissemination from the bloodstream to internal organs and evasion of immune responses and antibiotics. This was convincingly demonstrated MGCD0103 datasheet in a study of the role of FnBPA in experimental endocarditis where binding to both fibrinogen and fibronectin required. Binding of

fibrinogen was required for initial colonization of thrombi on damaged valves and while binding to fibronectin was required for the infection to spread [19]. FnBPA and FnBPB are encoded by two closely linked but separately transcribed genes, fnbA and fnbB [7, 9]. While most strains contain both genes, some strains contain only fnbA [20]. In strain 8325-4, studies with site-specific fnbA and fnbB insertion mutants showed that either FnBPA or FnBPB mediated adherence to immobilized fibronectin but there was no significant difference in adherence between wild type strains and https://www.selleckchem.com/products/ly2109761.html single fnb mutants [21]. However, studies with clinical isolates suggested that strain associated with

invasive diseases are significantly more likely to have two fnb genes [20]. Seven variants (isotypes I-VII) of FnBPA were identified based on divergence in the amino acid sequences of the minimal ligand-binding N23 sub-domains [22]. Each FnBPA isotype retained ligand-binding activity but were antigenically distinct. Modelling the 3D structures showed that the amino acid variation occurred in surface-exposed residues and not in those involved in ligand-binding [22]. The initial aim of this study was to characterize the A domain of FnBPB and to determine the extent of variation in the A domain. It was discovered that the A domain Branched chain aminotransferase of all FnBPB isotypes had the ability to bind to fibronectin by a novel mechanism. Results fnbB gene variation in S. aureus whole-genome sequences Previously we reported that the A domain of FnBPA from strain P1 varied substantially from that of strain 8325-4, sharing only 73.5% amino acid identity [11]. We then identified seven variants of FnBPA A domain (isotypes I-VII) based on divergence in the minimal ligand-binding N23 sub-domain. Each recombinant N23 variant was shown to retain ligand-binding function but was antigenically distinct [22]. This prompted us to investigate variation in the A domain of the second fibronectin-binding protein, FnBPB.