Staphylococcus aureus protein A enhances osteoclastogenesis via TNFR1 and EGFR signaling.

ANDREA C. MENDOZA BERTELLI; MARIA VICTORIA DELPINO; SANTIAGO LATTAR; CONSTANZA GIAI; MARIANGELES NOTO LLANA; NORBERTO SANJUAN; JAMES E. CASSAT; DANIEL SORDELLI; MARISA I. GOMEZ

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016

0925-4439

Staphylococcus aureus is a major causative agent of osteomyelitis in adults and children. The increasing incidence of antimicrobial resistant isolates and the morbidity ofthis type of infection denote that alternative therapeutic approaches are required. S.aureus protein A interacts with TNFR1 and EGFR expressed at the surface of host cells.Given the importance of TNF-α and EGFR/RANKL crosstalk in enhancing osteoclastdifferentiation, the aim of this study was to determine the role of protein A in theinduction of osteoclastogenesis and bone resorption during staphylococcalosteomyelitis. We determined that protein A plays a critical role in osteoclastdifferentiation and activation by initiating TNFR1 and EGFR mediated signaling.Moreover, we demonstrated that protein A significantly contributes to increasedosteoclast differentiation and activation as well as cortical bone destruction during thecourse of disease using experimental models of osteomyelitis. Our findings stronglysuggest targeting protein A and TNFR1 as an adjunctive strategy to control bonedamage during the initial course of S. aureus osteomyelitis.