Nguyen Fabian, Starosta Agata L, Arenz Stefan, Sohmen Daniel, Dönhöfer Alexandra, Wilson Daniel N
Biol Chem. 2014 May;395(5):559-75. doi: 10.1515/hsz-2013-0292.
The ribosome and protein synthesis are major targets within the cell for inhibition by antibiotics, such as the tetracyclines. The tetracycline family of antibiotics represent a large and diverse group of compounds, ranging from the naturally produced chlortetracycline, introduced into medical usage in the 1940s, to second and third generation semi-synthetic derivatives of tetracycline, such as doxycycline, minocycline and more recently the glycylcycline tigecycline. Here we describe the mode of interaction of tetracyclines with the ribosome and mechanism of action of this class of antibiotics to inhibit translation. Additionally, we provide an overview of the diverse mechanisms by which bacteria obtain resistance to tetracyclines, ranging from efflux, drug modification, target mutation and the employment of specialized ribosome protection proteins.
核糖体和蛋白质合成是细胞内抗生素抑制作用的主要靶点,比如四环素类抗生素。四环素类抗生素是一大类多样的化合物,从20世纪40年代引入医学用途的天然产生的金霉素,到四环素的第二代和第三代半合成衍生物,如强力霉素、米诺环素,以及最近的甘氨酰环素替加环素。在此,我们描述四环素与核糖体的相互作用模式以及这类抗生素抑制翻译的作用机制。此外,我们概述了细菌对四环素产生耐药性的多种机制,包括外排、药物修饰、靶点突变以及利用专门的核糖体保护蛋白。