Staphylococcus aureus Conquers Host by Hijacking Mitochondria via PFKFB3 in Epithelial Cells

Abstract

Abstract Staphylococcus aureus persists within mammary epithelial cells for an extended duration, exploiting the host metabolic resources to facilitate replication. This study revealed a mechanism by which intracellular S aureus reprograms host metabolism, with PFKFB3 playing a crucial role in this process. Mechanistically, S aureus induced mitochondrial damage, leading to increased levels of mitochondrial reactive oxygen species and dysfunction in the electron transport chain. Moreover, S aureus shifted the balance of mitochondrial dynamics from fusion to fission, subsequently activating PINK1-PRKN–dependent mitophagy, causing loss of sirtuin 3 to stabilize hypoxic inducible factor 1α, and shifting the host metabolism toward enhanced glycolysis. The inhibition of PFKFB3 reversed the mitochondrial damage and degradation of sirtuin 3 induced by S aureus. Overall, our findings elucidate the mechanism by which S aureus reprograms host metabolism, thereby offering insights into the treatment of S aureus infection.