PFKFB3-meditated glycolysis via ROS-HIF1α axis contributes to inflammation and proliferation of Staphylococcus aureus in epithelial cells.

Overview

Mastitis caused by antibiotic-resistant strains of Staphylococcus aureus (S. aureus) is a significant concern in the livestock industry due to the economic losses it incurs. Regulating immunometabolism has emerged as a promising approach for preventing bacterial inflammation. To investigate the possibility of alleviating inflammation caused by S. aureus infection by regulating host glycolysis, we subjected the murine mammary epithelial cell line (EpH4-Ev) to S. aureus challenge. Our study revealed that S. aureus can colonize EpH4-Ev cells and promote inflammation through HIF1α-driven glycolysis. Notably, the activation of HIF1α was found to be dependent on the production of reactive oxygen species (ROS). By inhibiting PFKFB3, a key regulator in the host glycolytic pathway, we successfully modulated HIF1α-triggered metabolic reprogramming by reducing ROS production in S. aureus-induced mastitis. Our findings suggest that there is a high potential for the development of novel anti-inflammatory therapies that safely inhibit the glycolytic rate-limiting enzyme PFKFB3.