Staphylococcus aureus protein A: a potential target to control bone loss in chronic osteomyelitis

ANDREA MENDOZA BERTELLI; M. VICTORIA DELPINO; SANTIAGO LATTAR; CONSTANZA GIAI; MARIANGELES NOTOLLANA; DANIEL SORDELLI; MARISA I.GOMEZ

Lucca

Conferencia; Staphylococcal Diseases- Gordon Research Conferences; 2015

Staphylococcus aureus is a major causative agent of osteomyelitis in adults. The increasing incidence of antimicrobial resistant isolates and the morbidity of this type of infection denote that alternative therapeutic approaches are required. S. aureus protein A interacts with TNFR1 mimicking TNF-a signaling. Considering that TNF-a signaling drives osteoclast differentiation, the aim of this study was to elucidate whether protein A may induce increased osteoclastogenesis and positively modulate bone resorption during S. aureus osteomyelitis. Using purified recombinant protein A as well as a pair of isogenic wild type USA300 and protein A deficient strains, we determined that protein A plays a critical role in osteoclast differentiation and activation in vitro. Moreover, we demonstrated that protein A significantly contributes to osteoclastogenesis and bone resorbing MMP-9 activity in vivo as well as tissue damage and bacterial persistence in the bone in an experimental model of osteomyelitis. Our findings strongly suggest targeting protein A as an alternative strategy to control bone damage and bacterial colonization during the initial course of S. aureus osteomyelitis.