The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis

Abstract

The importance of a collagen-binding adhesin in the pathogenesis of septic arthritis has been examined by comparing the virulence of two sets of Staphylococcus aureus mutants in an animal model. Collagen adhesin-negative mutant PH100 was constructed by replacing the chromosomal collagen adhesin gene (cna) in a clinical strain, Phillips, with an inactivated 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 functional analyses of the generated mutants and their respective parent strains showed that binding of 1251-labeled collagen, expression of an immunoreactive collagen adhesin, and bacterial adherence to cartilage were directly correlated with the presence of a functional cna gene. Greater than 70% of the mice injected with the Cna+ strains developed clinical signs of arthritis, whereas less than 27% of the animals injected with Cna-strains showed symptoms of disease. Furthermore, mice injected with the Cna+ strain Phillips had remarkably elevated levels of immunoglobulin Gl and interleukin-6 compared with mice injected with the Cnamutant PH100. Taken together, these results demonstrate that collagen adhesin plays an important role in the pathogenesis of septic arthritis induced by S. aureus.

Conditional adherence of Enterococcus faecalis to extracellular matrix proteins

“…Staphylococcus aureus may express several surface components for binding to collagen [17], ¢bronectin [18,19], ¢brinogen [20], vitronectin [21], thrombospondin [22], elastin [23], laminin [24] and bone sialoprotein [25]. Mutants of pathogenic streptococci and staphylococci isogenic except for MSCRAMM genes have shown reduced virulence in arthritis and infective endocarditis models [26,27].…”

Identification of the secreted macromolecular immunogens of Staphylococcus aureus by analysis of serum

“…An obvious question that needs to be addressed is how does S. aureus stimulate bone breakdown? The ability of S. aureus to adhere to components of the extracellular matrix found in bone has been shown to be important in experimental skeletal infections [5]. Our own work has established that amongst the secreted components produced by this organism are potent bone resorbing moieties [6], which have marked actions on osteoclast di¡erentiation [7] and activation [8].…”

The role of infectious agents in the pathogenesis of vasculitis

“…Variability in disease severity is a recognized feature of experimental as well as of human vasculitis. What modulates disease severity is still poorly understood, but antigen load 11 (and probably other antigen properties) 89 and the efficiency of the immune response might both play a role. IFN-g has been shown to be a key mediator of antigen-driven immune response in some experimental models 13,14 , but other mediators 15 are also implicated.…”