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.

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