Department of Molecular Biology, Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Int J Mol Sci. 2021 May 19;22(10):5356. doi: 10.3390/ijms22105356.
Bacteria have evolved an array of mechanisms enabling them to resist the inhibitory effect of antibiotics, a significant proportion of which target the ribosome. Indeed, resistance mechanisms have been identified for nearly every antibiotic that is currently used in clinical practice. With the ever-increasing list of multi-drug-resistant pathogens and very few novel antibiotics in the pharmaceutical pipeline, treatable infections are likely to become life-threatening once again. Most of the prevalent resistance mechanisms are well understood and their clinical significance is recognized. In contrast, ribosome protection protein-mediated resistance has flown under the radar for a long time and has been considered a minor factor in the clinical setting. Not until the recent discovery of the ATP-binding cassette family F protein-mediated resistance in an extensive list of human pathogens has the significance of ribosome protection proteins been truly appreciated. Understanding the underlying resistance mechanism has the potential to guide the development of novel therapeutic approaches to evade or overcome the resistance. In this review, we discuss the latest developments regarding ribosome protection proteins focusing on the current antimicrobial arsenal and pharmaceutical pipeline as well as potential implications for the future of fighting bacterial infections in the time of "superbugs."
细菌已经进化出一系列机制，使它们能够抵抗抗生素的抑制作用，而抗生素的很大一部分作用靶点是核糖体。事实上，几乎每一种目前在临床实践中使用的抗生素都已经确定了耐药机制。随着耐药性病原体的清单不断增加，而药物研发管道中几乎没有新的抗生素，可治疗的感染很可能再次变得危及生命。大多数流行的耐药机制都得到了很好的理解，其临床意义也得到了认可。相比之下，核糖体保护蛋白介导的耐药性长期以来一直没有被重视，并且在临床环境中被认为是一个次要因素。直到最近，在广泛的人类病原体中发现了 ABC 家族 F 蛋白介导的耐药性，核糖体保护蛋白的重要性才真正得到重视。了解潜在的耐药机制有可能指导开发新的治疗方法来规避或克服耐药性。在这篇综述中，我们讨论了核糖体保护蛋白的最新研究进展，重点关注当前的抗菌药物库和药物研发管道，以及在“超级细菌”时代对抗细菌感染的未来可能产生的影响。
