Vikedal Krister, Ræder Synnøve Brandt, Riisnæs Ida Mathilde Marstein, Bjørås Magnar, Booth James Alexander, Skarstad Kirsten, Helgesen Emily
Department of Microbiology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0373 Oslo, Norway.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7030 Trondheim, Norway.
Nucleic Acids Res. 2025 May 22;53(10). doi: 10.1093/nar/gkaf437.
Fluoroquinolones induce double-strand breaks in bacterial DNA, triggering the SOS response, a major DNA damage response that ensures the expression of repair proteins but also promotes the emergence and spread of antibiotic resistance. Fluoroquinolone resistance, particularly in Escherichia coli, is a growing global health concern. Understanding bacterial responses to these antibiotics is critical for developing preventive strategies and novel treatments to combat resistance development. This study investigates DNA morphology in E. coli following exposure to ciprofloxacin (CIP), a fluoroquinolone antibiotic. We show that CIP induces a stepwise DNA reorganization, culminating in a highly dense nucleoid structure at midcell-a process we term DNA supercompaction. This phenomenon occurred also with other genotoxic agents. Live-cell imaging revealed that RecN, a structural maintenance of chromosomes (SMC)-like protein, is required for DNA supercompaction, and that RecN's dynamics and activity in this response depend on RecA. Additionally, RecN and RecA frequently colocalized at nucleoid-associated positions. We suggest that RecN and RecA play active roles in DNA supercompaction following severe DNA damage, that their interplay is part of a prompt universal survival response to DNA double-strand breaks in E. coli, and that the extent of the compaction response depends on the DNA damage severity.
氟喹诺酮类药物可诱导细菌DNA双链断裂，触发SOS反应，这是一种主要的DNA损伤反应，既能确保修复蛋白的表达，也会促进抗生素耐药性的产生和传播。氟喹诺酮耐药性，尤其是在大肠杆菌中，是一个日益严重的全球健康问题。了解细菌对这些抗生素的反应对于制定预防策略和对抗耐药性发展的新疗法至关重要。本研究调查了大肠杆菌在接触氟喹诺酮类抗生素环丙沙星（CIP）后的DNA形态。我们发现，CIP诱导了一个逐步的DNA重组过程，最终在细胞中部形成高度致密的类核结构——我们将这一过程称为DNA超压缩。这种现象在其他基因毒性剂作用下也会发生。活细胞成像显示，RecN，一种类似染色体结构维持（SMC）的蛋白质，是DNA超压缩所必需的，并且RecN在这一反应中的动力学和活性依赖于RecA。此外，RecN和RecA经常在类核相关位置共定位。我们认为，RecN和RecA在严重DNA损伤后的DNA超压缩过程中发挥积极作用，它们的相互作用是大肠杆菌对DNA双链断裂的一种迅速的普遍生存反应的一部分，并且压缩反应的程度取决于DNA损伤的严重程度。
