对多种具有抗性的细菌病原体数量的令人不安的增加,或者有时全部,当前的抗生素凸显了迫切需要寻找和开发新型抗菌药物。有关细菌细胞分裂机制的丰富知识有助于靶标驱动的方法来鉴定新的抑制剂化合物。所追求的主要分裂目标是高度保守和必需的蛋白FtsZ。尽管几年来对FtsZ抑制剂的研究非常活跃,这种蛋白质尚未被任何商业抗生素靶向。这里,我们讨论了FtsZ作为药物开发的抗菌靶标的适用性,并回顾了该领域取得的进展。我们使用事后的观点来强调减缓FtsZ抑制剂开发进展的差距,并提出结论FtsZ实际上是这些分子的靶标的指南,在几项研究中缺失的关键一环。在前进中,多学科,交际,和协作过程,分享研究专业知识,如果我们要成功,至关重要。
The disturbing increase in the number of bacterial pathogens that are resistant to multiple, or sometimes all, current antibiotics highlights the desperate need to pursue the discovery and development of novel classes of antibacterials. The wealth of knowledge available about the bacterial cell division machinery has aided target-driven approaches to identify new inhibitor compounds. The main division target being pursued is the highly conserved and essential protein FtsZ. Despite very active research on FtsZ inhibitors for several years, this protein is not yet targeted by any commercial antibiotic. Here, we discuss the suitability of FtsZ as an antibacterial target for drug development and review progress achieved in this area. We use hindsight to highlight the gaps that have slowed progress in FtsZ inhibitor development and to suggest
guidelines for concluding that FtsZ is actually the target of these molecules, a key missing link in several studies. In moving forward, a multidisciplinary, communicative, and collaborative process, with sharing of research expertise, is critical if we are to succeed.