Immunometabolism shapes chronic Staphylococcus aureus infection: insights from biofilm infection models

Staphylococcus aureus is both a commensal bacterium and versatile pathogen, capable of transitioning from a benign colonizer to cause invasive disease. Its ability to form biofilm — a resilient, highly structured bacterial community — plays a key role in chronic infections, including those associated with medical implants and native tissues. The unique microenvironments of these biofilm niches create challenges for the host immune system, complicating pathogen clearance. Immunometabolism, the interplay between immune function and metabolic programming, plays a crucial role in dictating how the host combats S. aureus biofilms. Leukocytes undergo profound metabolic changes in response to biofilm, which can lead to dysregulated immune responses and persistent infection. This review explores recent insights defining the metabolic landscape of immune responses to S. aureus biofilm with a focus on two clinically relevant models, namely, craniotomy and prosthetic joint infection.