Surgical revision in the presence of an S. aureus infection increases virulence factor expression and activates a multi-tissue inflammatory response.

Replacing implanted medical hardware due to infection often requires one or more revision surgeries. Each surgery triggers a tissue injury response and disrupts the established bacterial biofilm. However, the complex tissue response to reinjury and biofilm disturbance is not well understood. Our results show that with an existing infection, immunological niches such as the bone marrow, lymph nodes, and circulating blood further upregulate pro-inflammatory programs in response to revision. Rather than reducing bacterial burden, this heightened inflammation provokes virulence factor expression and tissue damage, including bone osteolysis and muscle fibrosis. While muscle fibrosis appears transient and begins resolving by 14 days post-revision, osteolysis continues to progress. This study defines the timing and pathophysiology of coordinated multi-tissue responses to revision during infection. Understanding how host-pathogen interactions influence tissue recovery after revision can help identify risks and guide interventions that minimize damage and maximize bacterial clearance.