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

Internalization of Staphylococcus aureus (S. aureus) in 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 internalized S. aureus in osteoblasts was found in long bone of hematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalization rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor-FAK, phosphor-EGFR and phosphor-c-Src in a time dependent way, and blocking EGFR/FAK or c-Src signaling significantly reduced the internalization rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalization in osteoblast and raise the potential of targeting EGFR/FAK and c-Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis. This article is protected by copyright. All rights reserved.