Xiang Wen-Liang, Xiong Jie, Wang Han-Yang, Cai Ting, Shi Pei, Zhao Qiu-Huan, Tang Jie, Cai Yi-Min
Food Microbiology Key Laboratory of Sichuan Province, Xihua University, Chengdu, China.
School of Food and Bioengineering, Xihua University, Chengdu, China.
Front Microbiol. 2024 Nov 29;15:1505841. doi: 10.3389/fmicb.2024.1505841. eCollection 2024.
Toxin-antitoxin (TA) modules are important mediators of persister cell formation in response to environmental stresses. However, the mechanisms through which persistence is controlled remain poorly understood. , a novel probiotic, can enter a persistent state upon exposure to tetracycline stress. This study found that the Bro-Xre TA modules of function as typical tetracycline regulators. The Bro-Xre TA modules were activated when exposed to tetracycline stress, and the released toxin Bro acted on various cellular metabolic processes, including energy, amino acid, and nucleotide metabolism. Among them, the genes related to intracellular energy pathways, such as PTS, EMP, HMP, TCA, and oxidative phosphorylation, were downregulated, leading to reduced ATP synthesis and proton motive force. This metabolic disruption resulted in cells adopting a persistent phenotype, characterized by an increase in cell length in . Additionally, the frequency of persister cells increased under tetracycline stress. These results provide a novel perspective for understanding the mechanism by which TA modules induce persistence in probiotics, allowing them to evade antibiotic stress through metabolic disruption.
毒素 - 抗毒素（TA）模块是响应环境压力时持久细胞形成的重要介质。然而，控制持久性的机制仍知之甚少。一种新型益生菌在暴露于四环素压力下时可进入持久状态。本研究发现，该益生菌的Bro - Xre TA模块作为典型的四环素调节因子发挥作用。当暴露于四环素压力下时，Bro - Xre TA模块被激活，释放的毒素Bro作用于各种细胞代谢过程，包括能量、氨基酸和核苷酸代谢。其中，与细胞内能量途径相关的基因，如磷酸转移酶系统（PTS）、糖酵解途径（EMP）、磷酸戊糖途径（HMP）、三羧酸循环（TCA）和氧化磷酸化，均被下调，导致ATP合成和质子动力势降低。这种代谢紊乱导致细胞呈现持久表型，其特征是该益生菌细胞长度增加。此外，在四环素压力下，持久细胞的频率增加。这些结果为理解TA模块诱导益生菌持久性的机制提供了新的视角，使它们能够通过代谢紊乱逃避抗生素压力。
