Golkar Tolou, Zieliński Michał, Berghuis Albert M
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
Front Microbiol. 2018 Aug 20;9:1942. doi: 10.3389/fmicb.2018.01942. eCollection 2018.
Since their discovery in the early 1950s, macrolide antibiotics have been used in both agriculture and medicine. Specifically, macrolides such as erythromycin and azithromycin have found use as substitutes for β-lactam antibiotics in patients with penicillin allergies. Given the extensive use of this class of antibiotics it is no surprise that resistance has spread among pathogenic bacteria. In these bacteria different mechanisms of resistance have been observed. Frequently observed are alterations in the target of macrolides, i.e., the ribosome, as well as upregulation of efflux pumps. However, drug modification is also increasingly observed. Two classes of enzymes have been implicated in macrolide detoxification: macrolide phosphotransferases and macrolide esterases. In this review, we present a comprehensive overview on what is known about macrolide resistance with an emphasis on the macrolide phosphotransferase and esterase enzymes. Furthermore, we explore how this information can assist in addressing resistance to macrolide antibiotics.
自20世纪50年代初被发现以来，大环内酯类抗生素已在农业和医学领域得到应用。具体而言，红霉素和阿奇霉素等大环内酯类药物已被用作青霉素过敏患者的β-内酰胺类抗生素替代品。鉴于这类抗生素的广泛使用，耐药性在病原菌中传播也就不足为奇了。在这些细菌中，已观察到不同的耐药机制。常见的是大环内酯类药物靶点（即核糖体）的改变，以及外排泵的上调。然而，药物修饰现象也越来越多地被观察到。两类酶与大环内酯类药物解毒有关：大环内酯磷酸转移酶和大环内酯酯酶。在本综述中，我们全面概述了已知的大环内酯类耐药情况，重点介绍了大环内酯磷酸转移酶和酯酶。此外，我们还探讨了这些信息如何有助于应对大环内酯类抗生素耐药性问题。
