Li Rui-Rui, Yu Xiao-Jiao, Liang Jia-Yin, Sheng Jin-Liang, Zhang Hui, Chen Chuang-Fu, Ma Zhong-Chen, Wang Yong
College of Animal Science and Technology, Shihezi University, Shihezi 832000, China.
Biomolecules. 2025 Aug 1;15(8):1107. doi: 10.3390/biom15081107.
is an important pathogen that is associated with respiratory diseases, mastitis, and arthritis in cattle, leading to significant economic losses in the global cattle industry. Most notably in this study, we pioneer the discovery that its secreted effector ENO1 (α-enolase) directly targets host cytoskeletal proteins for metabolic-immune regulation. Using an innovative GST pull-down/mass spectrometry approach, we made the seminal discovery of β-actin (ACTB) as the primary host target of ENO1-the first reported bacterial effector-cytoskeleton interaction mediating metabolic reprogramming. ENO1-ACTB binding depends on a hydrogen bond network involving ACTB's 117Glu and 372Arg residues. This interaction triggers (1) glycolytic activation via Glut1 upregulation, establishing Warburg effect characteristics (lactic acid accumulation/ATP inhibition), and (2) ROS-mediated activation of dual inflammatory axes (HIF-1α/IL-1β and IL-6/TNF-α). This work establishes three groundbreaking concepts: (1) the first evidence of a pathogen effector hijacking host ACTB for metabolic manipulation, (2) a novel 'glycolysis-ACTB-ROS-inflammation' axis, and (3) the first demonstration of bacterial proteins coordinating a Warburg effect with cytokine storms. These findings provide new targets for anti-infection therapies against .
是一种重要的病原体，与牛的呼吸道疾病、乳腺炎和关节炎有关，给全球养牛业造成重大经济损失。在本研究中最值得注意的是，我们率先发现其分泌的效应蛋白ENO1（α-烯醇化酶）直接靶向宿主细胞骨架蛋白进行代谢免疫调节。使用创新的谷胱甘肽S-转移酶下拉/质谱方法，我们首次发现β-肌动蛋白（ACTB）是ENO1的主要宿主靶点——首次报道的介导代谢重编程的细菌效应蛋白-细胞骨架相互作用。ENO1-ACTB结合依赖于涉及ACTB的117Glu和372Arg残基的氢键网络。这种相互作用触发了（1）通过上调Glut1激活糖酵解，建立瓦伯格效应特征（乳酸积累/ATP抑制），以及（2）ROS介导的双炎症轴（HIF-1α/IL-1β和IL-6/TNF-α）的激活。这项工作确立了三个开创性的概念：（1）病原体效应蛋白劫持宿主ACTB进行代谢操纵的首个证据，（2）一个新的“糖酵解-ACTB-ROS-炎症”轴，以及（3）细菌蛋白协调瓦伯格效应与细胞因子风暴的首次证明。这些发现为针对……的抗感染治疗提供了新的靶点。
