EGFR/FAK and c-Src signaling pathways mediate the internalization of Staphylococcus aureus by osteoblasts.

Internalisation ofStaphylococcus aureusin osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalisedS. aureusin osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellularS. aureusby gentamicin can partially rescue bone loss, whereas the remaining intracellularS. aureusin osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellularS. aureuswas detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally,S. aureusinvasion stimulated the expression of phosphor-focal adhesion kinase (FAK), phosphor-epidermal growth factor receptor (EGFR) and phosphor-c-Src in a time-dependent way, and blocking EGFR/FAK or c-Src signalling significantly reduced the internalisation rate ofS. aureusin osteoblasts. Our findings provide new insights into the mechanism ofS. aureusinternalisation in osteoblast and raise the potential of targeting EGFR/FAK and c-Src as adjunctive therapeutics for treating chronicS. aureusosteomyelitis.