Shakil Shazi, Khan Rosina, Zarrilli Raffaele, Khan Asad U
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, 202002, Aligarh, India.
J Biomed Sci. 2008 Jan;15(1):5-14. doi: 10.1007/s11373-007-9194-y. Epub 2007 Jul 27.
Since 1944, we have come a long way using aminoglycosides as antibiotics. Bacteria also have got them selected with hardier resistance mechanisms. Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. There is an alarming increase in resistance outbreaks in hospital setting. Our review explores the molecular understanding of aminoglycoside action and resistance with an aim to minimize the spread of resistance.
自1944年以来,我们在使用氨基糖苷类抗生素方面已经取得了长足的进步。细菌也通过更强大的耐药机制对它们产生了选择。氨基糖苷类是氨基环醇类化合物,它们通过与16S核糖体RNA结合抑制蛋白质合成以及破坏细菌细胞膜的完整性来杀死细菌。氨基糖苷类耐药机制包括:(a)通过N-乙酰化、腺苷化或O-磷酸化使氨基糖苷类失活;(b)通过改变外膜通透性、减少内膜转运、主动外排和药物截留来降低氨基糖苷类在细胞内的浓度;(c)通过突变改变30S核糖体亚基靶点;(d)氨基糖苷类结合位点的甲基化。医院环境中耐药性爆发的情况令人担忧地增加。我们的综述探讨了对氨基糖苷类作用和耐药性的分子理解,旨在尽量减少耐药性的传播。