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 年的抗生素使用中，我们学到了很多关于这些“奇迹”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，以及对细菌结构、生理和复制的影响。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了如指掌。我们不知道的是最终的作用机制；也就是说，这些药物如何通过去除外部世界的障碍（细胞包膜）或破坏其遗传特性（DNA）来不可逆地终止细菌细胞的“个体性”。抗生素有许多不同的“作用机制”，它们会产生不可逆的致死效应。在这个视角下，