CONICET | Buscador de Institutos y Recursos Humanos

Staphylococcus aureus is a major causative agent of osteomyelitisin adults and children. The increasing incidence of antimicrobial resistantisolates and the morbidity of this type of infection denote thatalternative therapeutic approaches are required. We have recentlydemonstrated that staphylococcal protein A significantly contributesto increased osteoclast differentiation and activation as well as corticalbone destruction during the course of disease. Therefore, wehypothesize that targeting protein A in addition to antimicrobial treatmentcould be an adjunctive strategy to control bone damage duringthe initial course of S. aureus osteomyelitis. The aim of this studywas to evaluate the potential of using anti-protein A antibodies toneutralize the deleterious effect of this protein on bone homeostasisusing and in vivo experimental model of osteomyelitis. Groups ofBALB/c and C57BL/6 mice received anti-protein A antibodies by intraperitonealroute (75 mg/kg) or normal rabbit serum (sham control)one day before the subsequent challenge with S. aureus (2 x 106UFC) in the left tibia. Two days later the tibias were excised and thebone marrow cells collected and cultured in the presence of M-CSF(50 ng/ml) to obtain osteoclast precursors. Immunization with anti-protein A antibodies significantly reduced the priming of osteoclastprecursors in response to S. aureus infection as evidenced by theirdecreased capacity to differentiate into mature osteoclasts after invitro stimulation with RANKL (BALB/c: p<0,01; C57BL/6: p<0,001).Moreover, administration of anti-protein A antibodies on day -1, 6and 9 after S. aureus challenge significantly decreased the levelsof IL-1, IL-6 and TNF-α in the bone at day 14 after the onset ofexperimental osteomyelitis (p<0,05). These results indicate that anti-protein A antibodies could locally reduce the undesirable effectsof S. aureus induced osteoclastogenesis during the initial stages ofosteomyelitis.