Xiang Yuling, Zheng Jiachen, Liu Zhendong, Cui Xujie, Zhang Yunfan, Guo Minhao, Li Weihui
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.
Nucleic Acids Res. 2025 Jan 7;53(1). doi: 10.1093/nar/gkae1309.
Copper (Cu), a trace element with redox activity, is both essential and toxic to living organisms. Its redox properties make it a cofactor for a variety of proteins, but it also causes oxidative stress, hence the need to maintain intracellular copper homeostasis. However, the role of copper in the regulation of antioxidant defense in bacteria remains unclear, and the involved transcription factors remain to be explored. In this study, we identified a novel transcription factor, MscA, that responded directly to Cu2+ to regulate the antioxidant defense of mycobacteria. Cu2+ directly bound to MscA to mediate oxidation and inhibit the DNA binding activity of MscA, subsequently downregulating the expression of antioxidant gene cluster to increase the accumulation of reactive oxygen species in mycobacteria, ultimately leading to oxidative damage to mycobacteria. Therefore, we firstly reported that the Cu2+ responsive transcription factor regulated the antioxidant defense in bacteria. This finding firstly and directly links the function of Cu2+ to the antioxidant defense of bacteria, and provides a new insight into bacterial antioxidant defense.
铜（Cu）是一种具有氧化还原活性的微量元素，对生物体而言既是必需的，又具有毒性。其氧化还原特性使其成为多种蛋白质的辅助因子，但同时也会引发氧化应激，因此需要维持细胞内铜的稳态。然而，铜在细菌抗氧化防御调节中的作用仍不清楚，相关的转录因子也有待探索。在本研究中，我们鉴定出一种新型转录因子MscA，它直接响应Cu2+来调节分枝杆菌的抗氧化防御。Cu2+直接与MscA结合，介导氧化并抑制MscA的DNA结合活性，随后下调抗氧化基因簇的表达，从而增加分枝杆菌中活性氧的积累，最终导致分枝杆菌的氧化损伤。因此，我们首次报道了Cu2+响应转录因子调节细菌的抗氧化防御。这一发现首次直接将Cu2+的功能与细菌的抗氧化防御联系起来，为细菌抗氧化防御提供了新的见解。
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