CLINICAL AND MOLECULAR ASPECTS OF THE PATHOGENESIS OF STAPHYLOCOCCUS-AUREUS BONE AND JOINT INFECTIONS

Staphylococcus aureus is an important cause of bone and joint infectio ns. In recent years, significant changes in the incidence of septic ar thritis and osteomyelitis have occurred. Haematogenous osteomyelitis i s now less common during childhood, but secondary spread of infection to bone or joint from a contiguous site in adults is increasing in inc idence. Infection introduced at the time of surgery or arising by the haematogenous route is a significant complication of prosthetic joint implantation, and the effect of bone cement on local immune function m ay be important in this setting. Although S. epidermidis is a more com mon cause of prosthetic joint infection, S. aureus is more difficult t o treat. S. aureus produces a number of extracellular and cell-associa ted factors, but it is unclear what role these have as virulence facto rs in vivo. Furthermore, it is difficult in animal models to simulate transient bacteraemia followed by non-fulminating septic arthritis or osteomyelitis, as occurs in the patient. Surface factors which may be important in pathogenesis include the cell wall (activates complement and stimulates cytokine release), capsular polysaccharide (promotes ad hesion to host cell surfaces), collagen receptors and fibronectin-bind ing protein. Staphylococcal toxic shock syndrome toxin (TSST-1) and th e enterotoxins are superantigens and have the potential to suppress pl asma cell differentiation and antibody responsiveness. TSST-1-positive isolates have been shown to cause more severe joint infection in one animal model, but most other studies to date have focused on in-vitro rather than in-vivo effects. There is little evidence supporting a rol e for coagulase, lipase and the haemolysins in staphylococcal bone and joint infections. Despite the clinical importance of these infections , surprisingly little is known about pathogenesis at the cellular leve l. Future research should focus on the role of the host immune system in limiting spread of infection, and the expression of virulence facto rs in animal or other models incorporating isogenic mutant strains.