Staphylococcus aureus Conquers Host by Hijacking Mitochondria via PFKFB3 in Epithelial Cells
文献类型： 外文期刊
作者： Gao, Xing 1 ; Feng, Shiyuan 2 ; Wu, Binfeng 1 ; Liu, Laizhen 1 ; Xu, Yuanyuan 1 ; Zhang, Jinqiu 3 ; Miao, Jinfeng 1 ;
作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Minist Educ, Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210014, Peoples R China
2.Nanjing Agr Univ, Sanya Res Inst, Sanya, Peoples R China
3.Jiangsu Acad Agr Sci, Inst Vet Immunol & Engn, Nanjing, Peoples R China
4.Minist Sci & Technol, Jiangsu Key Lab Food Qual & Safety, State Key Lab Cultivat Base, Nanjing, Peoples R China
关键词： glycolysis; SIRT3-HIF1 alpha; mitophagy; PFKFB3; Staphylococcus aureus
期刊名称：JOURNAL OF INFECTIOUS DISEASES （ 影响因子：6.4； 五年影响因子：5.4 ）
ISSN： 0022-1899
年卷期： 2024 年
页码：
收录情况： SCI
摘要： 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 1 alpha, 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. Staphylococcus aureus induced sirtuin 3 degradation via mitophagy, thereby shifting metabolism toward glycolysis. Inhibition of PFKFB3 reduced mitochondrial damage by limiting reactive oxygen species production and alleviated the degradation of sirtuin 3.
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