Velkov Tony, Roberts Kade D, Li Jian
Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Australia.
Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, VIC, 3800, Australia.
Nat Prod Rep. 2017 Mar 17;34(3):295-309. doi: 10.1039/c6np00113k.
Covering: 1975 up to the end of 2016The decline in the discovery and development of novel antibiotics has resulted in the emergence of bacteria that are resistant to almost all available antibiotics. Currently, polymyxin B and E (colistin) are being used as the last-line therapy against life-threatening infections, unfortunately resistance to polymyxins in both the community and hospital setting is becoming more common. Octapeptins are structurally related non-ribosomal lipopeptide antibiotics that do not exhibit cross-resistance with polymyxins and have a broader spectrum of activity that includes Gram-positive bacteria. This makes them a precious and finite resource for the development of new antibiotics against these problematic polymyxin-resistant Gram-negative pathogens, in particular Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. This review surveys the progress in understanding octapeptin chemistry, mechanisms of antibacterial activity and biosynthesis. With the lack of cross-resistance and their broad antibacterial activity, the octapeptins represent ideal candidates for the development of a new generation of polymyxin-like lipopeptide antibiotics targeting polymyxin-resistant 'superbugs'.
1975年至2016年底
新型抗生素研发的减少导致了对几乎所有现有抗生素都具有抗性的细菌的出现。目前，多粘菌素B和E（黏菌素）被用作治疗危及生命感染的最后一线疗法，不幸的是，社区和医院环境中对多粘菌素的耐药性正变得越来越普遍。八肽菌素是结构相关的非核糖体脂肽抗生素，与多粘菌素不存在交叉耐药性，且具有包括革兰氏阳性菌在内的更广泛的活性谱。这使得它们成为开发针对这些有问题的耐多粘菌素革兰氏阴性病原体，特别是铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌的新型抗生素的宝贵且有限的资源。本综述调查了在理解八肽菌素化学、抗菌活性机制和生物合成方面的进展。由于缺乏交叉耐药性以及其广泛的抗菌活性，八肽菌素是开发针对耐多粘菌素“超级细菌”的新一代多粘菌素样脂肽抗生素的理想候选物。
