Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany.
Clausius Institute of Physical and Theoretical Chemistry, University of Bonn, Wegelerstr. 12, 53115 Bonn, Germany.
Sci Adv. 2023 Mar 22;9(12):eade9023. doi: 10.1126/sciadv.ade9023.
Bacterial cell wall biosynthesis is the target of many important antibiotics. Its spatiotemporal organization is closely coordinated with cell division. However, the role of peptidoglycan synthesis within cell division is not fully understood. Even less is known about the impact of antibiotics on the coordination of these two essential processes. Visualizing the essential cell division protein FtsZ and other key proteins in , we show that antibiotics targeting peptidoglycan synthesis arrest cell division within minutes of treatment. The glycopeptides vancomycin and telavancin completely inhibit septum constriction in all phases of cell division. The beta-lactam oxacillin stops division progress by preventing recruitment of the major peptidoglycan synthase PBP2 to the septum, revealing PBP2 as crucial for septum closure. Our work identifies cell division as key cellular target of these antibiotics and provides evidence that peptidoglycan synthesis is the essential driving force of septum constriction throughout cell division of .
细菌细胞壁生物合成是许多重要抗生素的作用靶点。其时空组织与细胞分裂密切协调。然而,肽聚糖合成在细胞分裂中的作用尚未完全了解。关于抗生素对这两个基本过程的协调作用,人们知之甚少。通过可视化靶向肽聚糖合成的关键细胞分裂蛋白 FtsZ 和其他关键蛋白,我们发现抗生素在治疗数分钟内即可阻断细胞分裂。糖肽万古霉素和替拉万星完全抑制所有细胞分裂阶段的隔膜收缩。β-内酰胺类药物苯唑西林通过阻止主要肽聚糖合成酶 PBP2 向隔膜募集来阻止分裂进程,表明 PBP2 对隔膜闭合至关重要。我们的工作确定了细胞分裂是这些抗生素的关键细胞靶标,并提供了证据表明,在 整个细胞分裂过程中,肽聚糖合成是隔膜收缩的基本驱动力。