THE STAPHYLOCOCCUS-AUREUS COLLAGEN ADHESIN IS A VIRULENCE DETERMINANTIN EXPERIMENTAL SEPTIC ARTHRITIS

The importance of a collagen-binding adhesin in the pathogenesis of se ptic arthritis has been examined by comparing the virulence of two set s of Staphylococcus aureus mutants in an animal model. Collagen adhesi n-negative mutant PH100 was constructed by replacing the chromosomal c ollagen adhesin gene (cna) in a clinical strain, Phillips, with an ina ctivated copy of the gene. Collagen adhesin-positive mutant S. aureus CYL574 was generated by introducing the cna gene into CYL316, a strain that normally lacks the cna gene. Biochemical, immunological, and fun ctional analyses of the generated mutants and their respective parent strains showed that binding of I-125-labeled collagen, expression of a n immunoreactive collagen adhesin, and bacterial adherence to cartilag e were directly correlated with the presence of a functional cna gene. Greater than 70% of the mice injected with the Cna(+) strains develop ed clinical signs of arthritis, whereas less than 27% of the animals i njected with Cna(-) strains showed symptoms of disease. Furthermore, m ice injected with the Cna(+) strain Phillips had remarkably elevated l evels of immunoglobulin G1 and interleukin-6 compared with mice inject ed with the Cna(-) mutant PH100. Taken together, these results demonst rate that collagen adhesin plays an important role in the pathogenesis of septic arthritis induced by S. aureus.