Department of Microbiology, Ramón y Cajal Institute for Health Research (IRYCIS), Ramón y Cajal University Hospital, Madrid, Spain.
Department of Biology, Emory University, Atlanta, GA, USA.
Nat Rev Microbiol. 2021 Feb;19(2):123-132. doi: 10.1038/s41579-020-00443-1. Epub 2020 Oct 6.
During the past 85 years of antibiotic use, we have learned a great deal about how these 'miracle' drugs work. We know the molecular structures and interactions of these drugs and their targets and the effects on the structure, physiology and replication of bacteria. Collectively, we know a great deal about these proximate mechanisms of action for virtually all antibiotics in current use. What we do not know is the ultimate mechanism of action; that is, how these drugs irreversibly terminate the 'individuality' of bacterial cells by removing barriers to the external world (cell envelopes) or by destroying their genetic identity (DNA). Antibiotics have many different 'mechanisms of action' that converge to irreversible lethal effects. In this Perspective, we consider what our knowledge of the proximate mechanisms of action of antibiotics and the pharmacodynamics of their interaction with bacteria tell us about the ultimate mechanisms by which these antibiotics kill bacteria.
在过去 85 年的抗生素使用过程中，我们已经了解了很多关于这些“神奇”药物如何发挥作用的知识。我们知道这些药物及其靶点的分子结构和相互作用，以及它们对细菌结构、生理学和复制的影响。总的来说，我们对目前使用的几乎所有抗生素的这些近似作用机制都有了很多了解。我们不知道的是最终的作用机制；也就是说，这些药物如何通过消除细菌细胞与外界之间的障碍（细胞壁）或破坏其遗传特性（DNA），不可逆转地终止细菌细胞的“个体性”。抗生素有许多不同的“作用机制”，这些机制汇聚在一起产生不可逆转的致死效应。在本观点中，我们考虑了我们对抗生素的近似作用机制和它们与细菌相互作用的药效动力学的了解，这些了解告诉我们这些抗生素杀死细菌的最终机制。
