Spero Therapeutics, 675 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Infect Dis. 2020 Jun 12;6(6):1323-1331. doi: 10.1021/acsinfecdis.0c00025. Epub 2020 Mar 25.
The prospect of ever increasing antibiotic resistance eroding currently available treatment options for bacterial infections underscores the need to continue to identify new antibiotics, preferably those that act on novel targets or with novel mechanisms of action. Bacterial gyrase B subunit (GyrB), an essential component of bacterial gyrase required for successful DNA replication, represents such a target. We describe recent examples of GyrB inhibitors and point out their potential utility for treatment of mycobacterial diseases caused by (TB) and non-tuberculous mycobacteria (NTM). Current therapeutic options for these diseases are often suboptimal due to resistance to current standard of care antibiotics. A future GyrB inhibitor-based antibiotic could offer a new and effective addition to the armamentarium for treatment of mycobacterial diseases and possibly for infections caused by other bacterial pathogens. One GyrB inhibitor, SPR720, has recently completed a first-in-human clinical trial and is in clinical development for the treatment of NTM and TB infections.
不断增加的抗生素耐药性使目前用于治疗细菌感染的治疗方案受到侵蚀，这突显出需要继续寻找新的抗生素，最好是那些针对新靶点或具有新作用机制的抗生素。细菌拓扑异构酶 B 亚基（GyrB）是细菌拓扑异构酶必需的组成部分，是成功复制 DNA 所必需的，是这样的一个靶点。我们描述了 GyrB 抑制剂的最新实例，并指出它们在治疗结核分枝杆菌（TB）和非结核分枝杆菌（NTM）引起的疾病方面的潜在用途。由于目前的标准护理抗生素产生耐药性，这些疾病的当前治疗选择往往并不理想。基于 GyrB 抑制剂的抗生素可能成为治疗分枝杆菌病的新的有效手段，也可能成为治疗其他细菌病原体感染的手段。一种 GyrB 抑制剂 SPR720 最近完成了首次人体临床试验，目前正在开发用于治疗 NTM 和 TB 感染。
