A novel antibacterial immune activator: Bi-MOF acts as H2S scavenger to suppress HIF-1α S-sulfhydration and alleviate implant-associated infection

Abstract

Implant-associated infection (IAI) has significantly impeded the progress of surgery, and a properly functioning antibacterial immune response is critical for preventing persistent infection and reinfection. However, the efficacy of current infection immunotherapy remains considerably suboptimal, primarily because of the lack of validated therapeutic targets and interventions. Herein, we identify a bismuth-based metal organic frameworks (Bi-MOF) as an efficient intracellular hydrogen sulfide (H2S) scavenger that promotes the antibacterial response of macrophages through the inhibition of hypoxia inducible factor-1α (HIF-1α) S-sulfhydration and subsequent ubiquitin-dependent degradation. The reduction in H2S levels by Bi-MOF in vivo contributes to accelerated the clearance of bacteria, prevention of bone destruction, and augmentation of innate immunity in a mouse IAI model. Moreover, Bi-MOF also boost bacteria-specific adaptive immunity, thereby generating long-lasting protection against reinfection. Together, our results demonstrate that H2S-responsive Bi-MOF offer a promising immunotherapeutic approach as a potential alternative to antibiotics for managing stubborn IAIs.