Zorrilla Silvia, Monterroso Begoña, Robles-Ramos Miguel-Ángel, Margolin William, Rivas Germán
Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain.
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas, Houston, TX 77030, USA.
Antibiotics (Basel). 2021 Mar 4;10(3):254. doi: 10.3390/antibiotics10030254.
FtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a "divisome", FtsZ is a leading target in the quest for new antibacterial compounds. Strategies to potentially arrest the essential and tightly regulated cell division process include perturbing FtsZ's ability to interact with itself and other divisome proteins. Here, we discuss the available methodologies to screen for and characterize those interactions. In addition to assays that measure protein-ligand interactions in solution, we also discuss the use of minimal membrane systems and cell-like compartments to better approximate the native bacterial cell environment and hence provide a more accurate assessment of a candidate compound's potential in vivo effect. We particularly focus on ways to measure and inhibit under-explored interactions between FtsZ and partner proteins. Finally, we discuss recent evidence that FtsZ forms biomolecular condensates in vitro, and the potential implications of these assemblies in bacterial resistance to antibiotic treatment.
FtsZ是大多数细菌细胞分裂所必需的核心蛋白。由于其能够在细胞膜上组装成动态聚合物并招募其他蛋白质伙伴形成“分裂体”,FtsZ是寻找新型抗菌化合物的主要靶点。潜在阻止这一必需且严格调控的细胞分裂过程的策略包括干扰FtsZ与自身及其他分裂体蛋白相互作用的能力。在此,我们讨论用于筛选和表征这些相互作用的现有方法。除了测量溶液中蛋白质-配体相互作用的检测方法外,我们还讨论了使用最小膜系统和类细胞区室来更好地模拟天然细菌细胞环境,从而更准确地评估候选化合物的体内潜在效应。我们特别关注测量和抑制FtsZ与伙伴蛋白之间尚未充分研究的相互作用的方法。最后,我们讨论了最近的证据表明FtsZ在体外形成生物分子凝聚物,以及这些聚集体对细菌抗生素治疗抗性的潜在影响。