Cell metabolism · 2025
Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation.
СтатьяНазвание и аннотация: Перевод в очереди
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Cheng Zhou-Li, Zhang Shuyuan, Wang Zhenning, Song Aixia, Gao Chao, Song Jun-Bin, Wang Pu, Zhang Lei, Zhou Yue, Shan Wenyan, Zhang Chen, Zhang Jinye, Sun Yiping, Xu Yanhui, Lan Fei, Zhong Ming, Lyu Liang-Dong, Huang Guanghua, Chen Fei Xavier, Li Gang, Wang Zixin, Chen Faying, Xue Jianhuang, Shi Jiejun, Liu Yujun, Lin Zihao, Wu Duojiao, Na Jim, Chen Lei-Lei, Guan Kun-Liang, Xiong Yue, Ye Dan
Аннотация
Pathogenic bacterial persistence enables survival during antibiotic treatment, leading to treatment failure and recurrent infections, yet its underlying mechanisms remain unclear. Here, we reveal that glyoxylate, a metabolite originally evolved for alternative carbon utilization, functions as a signaling molecule to reprogram the host transcriptome and promote persister formation. Glyoxylate inhibits the DNA dioxygenase TET2, suppressing pro-inflammatory gene expression and attenuating host immune defense. Notably, stimulating TET2 activity with vitamin C or blocking glyoxylate production by Salmonella reduces bacterial antibiotic resistance and improves infection treatment outcomes. Beyond its metabolic role, glyoxylate emerges as a regulator of host-pathogen interactions, while TET2 plays a critical role in preventing bacterial persistence. Our findings suggest that targeting glyoxylate production or enhancing TET2 activity offers promising therapeutic strategies to combat bacterial persistence and enhance the efficacy of antibiotic treatments.