Proximate and ultimate causes of the bactericidal action of antibiotics

被引:183
作者
Baquero, Fernando [1 ]
Levin, Bruce R. [2 ,3 ]
机构
[1] Ramon y Cajal Univ Hosp, Ramon y Cajal Inst Hlth Res IRYCIS, Dept Microbiol, Madrid, Spain
[2] Emory Univ, Dept Biol, Atlanta, GA 30322 USA
[3] Emory Univ, Antibiot Resistance Ctr, Atlanta, GA 30322 USA
关键词
BETA-LACTAM ANTIBIOTICS; ESCHERICHIA-COLI; CELL-DEATH; PROTEIN-SYNTHESIS; STAPHYLOCOCCUS-AUREUS; RIBOSOMAL-BINDING; RNA-POLYMERASE; SOS RESPONSE; MECHANISM; MEMBRANE;
D O I
10.1038/s41579-020-00443-1
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. We know a lot about antibiotics and their targets; however, how antibiotics actually kill bacteria is not entirely clear and is up for debate. In this Perspective, Baquero and Levin reflect on this ultimate action of antibiotics and consider different mechanisms and modulating factors.
引用
收藏
页码:123 / 132
页数:10
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