Staphylococcus aureus blocks host autophagy through circSyk/miR-5106/Sik3 axis to promote progression of bone infection

PLoS Pathog. 2025 Jan 27;21(1):e1012896. doi: 10.1371/journal.ppat.1012896. Online ahead of print.

Abstract

With the rapid increase in the number of implant operations, the incidence of bone infections has increased. Methicillin-resistant Staphylococcus aureus (S. aureus) and other emerging fully drug-resistant strains make the management of bone infections even more challenging. Bone infections are mainly caused by S. aureus and require extensive surgical intervention and long-term antibiotic therapy. The host autophagy response is critical to the elimination of S. aureus infections. In this study, we demonstrate that a circular RNA (circRNA), circSyk, is a potential biological target for the treatment of S. aureus-induced bone infection. Most importantly, S. aureus regulates circSyk to block autophagy and promote bone destruction via the circSyk/miR-5106/Sik3 axis in a nonclassical pathway, which is involved in the S. aureus infection process through a competitive endogenous RNA network. In summary, this study proposes a novel perspective on the immune escape of S. aureus in bone infections, based on circRNA.