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 tissues. 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 variability within the Fn-binding domain of the FnBP adhesins and evaluate factors that promote variance in Fn binding among clinical isolates. Based on variation in the number of fnb genes or the number of D motifs, we identified five 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 gene with only two D motifs and was associated with the epidemic CMRSA-4 strain, which exhibited high protease activity and low Fn binding. Polymorphism group III was unique to the epidemic CMRSA-1 strain, defined by the presence of a fourth D motif that exhibited antigenic variation within a conserved 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 protease 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 variation 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.
Rice
K
K
University of Toronto, Department of Laboratory Medicine and Pathobiology, and Sunnybrook and Women's College Health Science Center, Department of Microbiology, Toronto, Ontario M4N 3M5, Canada.
Huesca
M
M
Vaz
D
D
McGavin
M J
MJ
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000940:Antigenic Variation; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004196:Disease Outbreaks; D010450:Endopeptidases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D016106:Methicillin Resistance; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018829:Adhesins, Bacterial; C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D015534:Trans-Activators; D014157:Transcription Factors; C078635:fibronectin-binding proteins, bacterial; D010450:Endopeptidases