Variance in fibronectin binding and fnb locus polymorphisms in Staphylococcus aureus: Identification of antigenic variation in a fibronectin binding protein adhesin of the epidemic CMRSA-1 strain of methicillin-resistant S-aureus

The fnbA and fnbB genes of Staphylococcus aureus 8325-4 encode fibronectin (Fn) binding proteins FnBPA and FnBPB, which promote adherence to host tiss ues. Each adhesin contains three copies of a repeated D motif that binds Fn and is a target for vaccine development. In this study, we assess variabil ity within the Fn-binding domain of the FnBP adhesins and evaluate factors that promote variance in Fn binding among clinical isolates. Based on varia tion in the number of fnb genes or the number of D motifs, we identified fi ve polymorphism groups. S. aureus 8325-4 and 91% of methicillin-resistant S . aureus (MRSA) isolates belong to polymorphism group I, with two fnb genes and three copies of the D motif. Polymorphism group II contained one fnb g ene with only two D motifs and was associated with the epidemic CMRSA-4 str ain, which exhibited high protease activity and low Fn binding. Polymorphis m group III was unique to the epidemic CMRSA-1 strain, defined by the prese nce of a fourth D motif that exhibited antigenic variation within a conserv ed sequence that is essential for Fn binding. However, the sequence of the D motifs was otherwise highly conserved among the other polymorphism groups . Variation in Fn binding among MRSA isolates was inversely related to prot ease activity but not to the number of fnb genes or the number of D motifs. Therefore, the fnb locus is polymorphic in a small number of strains, but this does not contribute to variation in Fn binding. The antigenic variatio n that was observed only in the epidemic CMRSA-1 strain may have evolved in response to a host immune response encountered during successive cycles of colonization, transmission, and infection in the nosocomial environment.