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

by Zhihao Chen, Qiyuan Jin, Jinqi Zhong, Zonggang Xie, Qi Chen, Liubing Li, Jijie Li, Chenhao Zhao, Junfeng Wang, Xiaoying Tang, Mingxiao Han, Ru Li, Ziyuan Li, Zelei Tong, Min Wang, Hong Du, Haifang Zhang

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.