放线菌来源的糖肽类抗生素的药学机制研究进展

Advances in pharmacological mechanism of glycopeptide antibiotics from actinomycetes

糖肽类抗生素具有较好的抑制革兰氏阳性细菌生长的活性,临床上广泛用于治疗革兰氏阳性细菌导致的严重感染性疾病,也被认为是对抗这类顽固性病原菌的最后一道防线。随着耐药菌的不断涌现,糖肽类抗生素的应用越来越受到限制。本文针对糖肽类抗生素的结构特征与药效关系、生物学活性和病原菌对于它们的耐药机制,以及糖肽类抗生素的生物合成机制及其结构的合成生物学改造等方面进行了概述。最后,对糖肽类抗生素在应用中面临的问题进行了展望。

Glycopeptide antibiotics have potent inhibition of gram positive bacteria. They are also as the last line of defense for dealing with the serious infections caused by such bacteria. As the drug-resistant pathogens spread, the application of glycopeptide antibiotics becomes more and more restricted. In this review, the structural characteristic of glycopeptide antibiotics and their structure-bioactivity relationship, the mechanism of biological activity and resistance for pathogenic bacteria of glycopeptide antibiotics were summarized. Furthermore, the biosynthetic mechanism and targeted generation of novel glycopeptide antibiotics by synthetic biology strategy for clinical application was also discussed. Finally, the problems in the glycopeptide antibiotic application were prospected.