Nutrient starvation usually halts cell growth rather than causing death. Thymine starvation is exceptional, because it kills cells rapidly. This phenomenon, called thymineless death (TLD), underlies the action of several antibacterial, antimalarial, anticancer, and immunomodulatory agents. Many explanations for TLD have been advanced, with recent efforts focused on recombination proteins and replication origin (oriC) degradation. Because current proposals account for only part of TLD and because reactive oxygen species (ROS) are implicated in bacterial death due to other forms of harsh stress, we investigated the possible involvement of ROS in TLD. Here, we show that thymine starvation leads to accumulation of both single-stranded DNA regions and intracellular ROS, and interference with either event protects bacteria from double-stranded DNA breakage and TLD. Elevated levels of single-stranded DNA were necessary but insufficient for TLD, whereas reduction of ROS to background levels largely abolished TLD. We conclude that ROS contribute to TLD by converting single-stranded DNA lesions into double-stranded DNA breaks. Participation of ROS in the terminal phases of TLD provides a specific example of how ROS contribute to stress-mediated bacterial self-destruction.

中文翻译：

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活性氧对大肠杆菌中无胸腺嘧啶死亡的贡献。

营养不足通常会阻止细胞生长，而不是导致死亡。胸腺嘧啶饥饿是例外，因为它会迅速杀死细胞。这种现象称为无胸腺嘧啶死亡（TLD），是多种抗菌，抗疟疾，抗癌和免疫调节剂作用的基础。已经提出了许多有关TLD的解释，最近的努力集中在重组蛋白和复制起点（oriC）降解上。由于当前的提议仅占TLD的一部分，并且由于其他形式的苛刻胁迫导致活性氧与细菌死亡有关，因此我们研究了ROS在TLD中的可能参与。在这里，我们显示胸腺嘧啶饥饿导致单链DNA区域和细胞内ROS的积累，对这两种情况的干扰都可以保护细菌免受双链DNA断裂和TLD的侵害。升高单链DNA的水平是必要的，但对于TLD而言却不足，而将ROS降低至背景水平在很大程度上废除了TLD。我们得出结论，ROS通过将单链DNA损伤转化为双链DNA断裂而有助于TLD。ROS在TLD末端阶段的参与提供了ROS如何促进应激介导的细菌自我毁灭的一个具体例子。