Staphylococcus aureus - induced tumor necrosis factor - related apoptosis - inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts

Normal osteoblasts were incubated in the presence of purified bacterial products over a range of concentrations. Results demonstrate that purified surface structures and a selected superantigen present in the extracellular environment are not capable of inducing TRAIL expression by osteoblasts. Osteoblasts were co-cultured with S. aureus at various multiplicities of infection utilizing cell culture chamber inserts. Results of those experiments suggest that direct contact between bacteria and osteoblasts is necessary for optimal TRAIL induction. Finally, S. aureus infection of osteoblasts in the presence of anti-TRAIL antibody demonstrates that TRAIL mediates caspase-8 activation and apoptosis of infected cells.Collectively, these findings suggest a mechanism whereby S. aureus mediates bone destruction via induction of osteoblast apoptosis.Staphylococcus aureus is the most common cause of osteomyelitis, a disease often refractory to treatment and subject to recurrence. Traditional treatment for osteomyelitis involves surgical debridement of infected tissue, coupled with systemic antibiotic therapy. Only a few decades ago, the majority of S. aureus strains associated with osteomyelitis were susceptible to antibiotics including methicillin. However, the emergence of antibiotic resistance among strains of S. aureus has rendered methicillin and many other antibiotics less effective against this organism. Consequently, there is an urgent need for the development of novel therapies for the treatment of osteomyelitis.S. aureus is a capable bone pathogen, in part, because it possesses several cell surface adhesion molecules that facilitate its binding to bone matrix. Binding involves a family of adhesins that interact with extracellular matrix components, and these adhesins have been termed microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) [1]. Specific MSCRAMMs are responsible for localization of S. aureus to particular tissues, and include fibro