Involvement of mitogen-activated protein kinase pathways in Staphylococcusaureus invasion of normal osteoblasts

Staphylococcus aureus invades osteoblasts and can persist in the intracellu lar environment. The present study examined the role of osteoblast mitogen- activated protein kinase (MAPK) pathways in bacterial invasion. S. aureus i nfection of normal human and mouse osteoblasts resulted in an increase in t he phosphorylation of the extracellular signal-regulated protein kinases (E RK 1 and 2). This stimulation of ERK 1 and 2 correlated with the time cours e of S. aureus invasion, and bacterial adherence induced the MAPK pathway. ERK 1 and 2 phosphorylation was time and dose dependent and required active S. aureus gene expression for maximal induction. The nonpathogenic Staphyl ococcus carnosus was also able to induce ERK 1 and 2 phosphorylation, albei t at lower levels than S. aureus. Phosphorylation of the stress-activated p rotein kinases was increased in both infected human and mouse osteoblasts; however, the p38 MAPK pathway was not activated in response to S. aureus. F inally, the transcription factor c-Jun, but not Elk-1 or ATF-2, was phospho rylated in response to S. aureus infection.