Zhang Yuzhen, Cai Yumin, Jin Xin, Wu Qile, Bai Fan, Liu Jintao
Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Beijing, China.
Nat Chem Biol. 2025 Feb;21(2):238-246. doi: 10.1038/s41589-024-01708-z. Epub 2024 Aug 13.
Antibiotics typically induce major physiological changes in bacteria. However, their effect on nutrient consumption remains unclear. Here we found that Escherichia coli communities can sustain normal levels of glucose consumption under a broad range of antibiotics. The community-living resulted in a low membrane potential in the bacteria, allowing slow antibiotic accumulation on treatment and better adaptation. Through multi-omics analysis, we identified a prevalent adaptive response characterized by the upregulation of lipid synthesis, which substantially contributes to sustained glucose consumption. The consumption was maintained by the periphery region of the community, thereby restricting glucose penetration into the community interior. The resulting spatial heterogeneity in glucose availability protected the interior from antibiotic accumulation in a membrane potential-dependent manner, ensuring rapid recovery of the community postantibiotic treatment. Our findings unveiled a community-level antibiotic response through spatial regulation of metabolism and suggested new strategies for antibiotic therapies.
抗生素通常会引起细菌的主要生理变化。然而，它们对营养物质消耗的影响仍不清楚。在这里，我们发现大肠杆菌群落可以在广泛的抗生素环境下维持正常水平的葡萄糖消耗。群落生活导致细菌的膜电位较低，使得在治疗过程中抗生素积累缓慢，从而具有更好的适应性。通过多组学分析，我们确定了一种以脂质合成上调为特征的普遍适应性反应，这对持续的葡萄糖消耗有很大贡献。葡萄糖消耗由群落的外围区域维持，从而限制了葡萄糖渗透到群落内部。由此产生的葡萄糖可利用性的空间异质性以膜电位依赖的方式保护内部免受抗生素积累，确保群落抗生素治疗后快速恢复。我们的研究结果揭示了通过代谢的空间调节产生的群落水平抗生素反应，并提出了抗生素治疗的新策略。
