A Pilot Study of Mitochondrial Response to an In Vivo Prosthetic Joint Staphylococcus aureus Infection Model.

Prosthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the "cell's powerhouses," are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune-infection interactions potentially hinder patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant-associated in vivo model, tissues were harvested from the surgical limb of a methicillin-sensitive Staphylococcus aureus implant-associated infection group (n=6) and compared to a non-infected group (n=6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus non-infected groups. On POD21, colony forming units per gram of tissue showed 5x10 9 in the infected group and 10 1 in the non-infected group (p<0.0001). Maximal respiration and oxygen consumption due to ATP synthesis were significantly lower in isolated mitochondria from infected limbs (p=0.04). Both groups had similar complex I, III, IV, and V activity (p>0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31±0.30 compared to 1.16±0.28 (p=0.73) in the non-infected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI. This article is protected by copyright. All rights reserved.