Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
Cell Mol Life Sci. 2010 Feb;67(3):419-31. doi: 10.1007/s00018-009-0172-6. Epub 2009 Oct 28.
Resistance to tetracycline emerged soon after its discovery six decades ago. Extensive clinical and non-clinical uses of this class of antibiotic over the years have combined to select for a large number of resistant determinants, collectively termed the tetracycline resistome. In order to impart resistance, microbes use different molecular mechanisms including target protection, active efflux, and enzymatic degradation. A deeper understanding of the structure, mechanism, and regulation of the genes and proteins associated with tetracycline resistance will contribute to the development of tetracycline derivatives that overcome resistance. Newer generations of tetracyclines derived from engineering of biosynthetic genetic programs, semi-synthesis, and in particular recent developments in their chemical synthesis, together with a growing understanding of resistance, will serve to retain this class of antibiotic to combat pathogens.
六十年前，四环素问世不久，就出现了耐药性。多年来，该类抗生素在临床和非临床方面的广泛应用，共同选择了大量的耐药决定因素，统称为四环素耐药组。为了产生耐药性，微生物使用不同的分子机制，包括靶标保护、主动外排和酶降解。深入了解与四环素耐药性相关的基因和蛋白质的结构、机制和调控，将有助于开发克服耐药性的四环素衍生物。通过生物合成遗传程序工程、半合成以及特别是最近在化学合成方面的进展，从新一代四环素中衍生而来，再加上对耐药性的不断深入了解，将有助于保留这类抗生素来对抗病原体。
