SORDELLI Daniel Oscar
congresos y reuniones científicas
Staphylococcus aureus protein A: a potential target to control bone loss in chronic osteomyelitis.
MENDOZA BERTELLI A; DELPINO MV; SORDELLI DO; GOMEZ MI
Conferencia; Gordon Research Conference, Staphylococcal Diseases.; 2015
Gordon Research Conference
Staphylococcus aureus is a major causative agent of osteomyelitis inadults. The increasing incidence of antimicrobial resistant isolates and themorbidity of this type of infection denote that alternative therapeuticapproaches are required. S. aureus protein A interacts with TNFR1 mimickingTNF-α signaling. Considering that TNF-αsignaling drives osteoclast differentiation, the aim of this study was toelucidate whether protein A may induce increased osteoclastogenesis andpositively modulate bone resorption during S. aureus osteomyelitis. Usingpurified recombinant protein A as well as a pair of isogenic wild type USA300and protein A deficient strains, we determined that protein A plays a criticalrole in osteoclast differentiation and activation in vitro. Moreover, wedemonstrated that protein A significantly contributes to osteoclastogenesis andbone resorbing MMP-9 activity in vivo as well as tissue damage and bacterialpersistence in the bone in an experimental model of osteomyelitis. Our findingsstrongly suggest targeting protein A as an alternative strategy to control bonedamage and bacterial colonization during the initial course of S. aureusosteomyelitis.