Bactericidal antibiotics can cause metabolic perturbations that contribute to antibiotic-induced lethality. The molecular mechanism underlying these downstream effects remains unknown. Here, we show that ofloxacin, a fluoroquinolone that poisons DNA gyrase, induces a cascade of metabolic changes that are dependent on an active SOS response. We identified the SOS-regulated TisB protein as the unique molecular determinant responsible for cytoplasmic condensation, proton motive force dissipation, loss of pH homeostasis, and H₂O₂ accumulation in Escherichia coli cells treated with high doses of ofloxacin. However, TisB is not required for high doses of ofloxacin to interfere with the function of DNA gyrase or the resulting rapid inhibition of DNA replication and lethal DNA damage. Overall, the study sheds light on the molecular mechanisms by which ofloxacin affects bacterial cells and highlights the role of the TisB protein in mediating these effects.

中文翻译：

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TisB 蛋白是氧氟沙星在大肠杆菌中产生多种下游效应的单分子决定因素

杀菌抗生素会引起代谢紊乱，从而导致抗生素引起的死亡。这些下游效应背后的分子机制仍然未知。在这里，我们发现氧氟沙星（一种毒害 DNA 旋转酶的氟喹诺酮类药物）会诱导一系列依赖于活跃 SOS 反应的代谢变化。我们确定 SOS 调节的 TisB 蛋白是导致高剂量氧氟沙星处理的大肠杆菌细胞中细胞质凝聚、质子动力耗散、pH 稳态丧失和 H ₂ O ₂积累的独特分子决定因素。然而，高剂量的氧氟沙星不需要 TisB 来干扰 DNA 旋转酶的功能或由此产生的 DNA 复制快速抑制和致命的 DNA 损伤。总体而言，该研究揭示了氧氟沙星影响细菌细胞的分子机制，并强调了 TisB 蛋白在介导这些影响中的作用。