Department of Structural Biology, Weizmann Institute, Rehovot 76100, Israel.
Antibiotics (Basel). 2016 Jun 29;5(3):24. doi: 10.3390/antibiotics5030024.
Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.
大多数核糖体抗生素会阻碍核糖体的特定功能。在某些情况下,除了使重要的核糖体任务瘫痪外,一些核糖体抗生素还参与细胞调节。由于致病性细菌菌株中多药耐药性的全球迅速增加,以及全球新抗生素的开发进展非常缓慢,除了传统的改进现有抗生素和密集筛选额外的天然化合物的尝试外,该领域似乎需要进行实质性的概念修正。在这里,我们强调了几个当代问题,包括挑战广谱抗生素的常见偏好;对抗生素使用导致微生物组种群变化的关注不足,以及对抗生素使用的生态和环境方面的认识不足。我们还强调了最近在鉴定可能用于设计和创造新型、环保、可降解的抗生素类型的物种特异性结构基序方面的进展,这些类型的抗生素可以更好地区分微生物组中的病原体和有用的细菌物种。因此,这些研究正在朝着设计“针对病原体的抗生素”的方向发展,与当前广谱抗生素的偏好形成对比,部分原因是需要在加速发现独特的物种基序以及临床病原体鉴定方面做出重大努力。