Aminoglycoside modifying enzymes.
Aminoglycoside modifying enzymes.
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DOI：
10.1016/j.drup.2010.08.003
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发表时间：
2010-12
影响因子：
24.3
通讯作者：
Tolmasky, Marcelo E.
中科院分区：
文献类型：
--
作者：
Ramirez, Maria S.;Tolmasky, Marcelo E.
关键词：
氨基糖苷类药物一直是治疗危及生命的感染的重要组成部分。不幸的是，它们的效力因耐药性的激增和传播而降低。在某些情况下，抵抗的程度达到了几乎使它们无用的程度。在许多已知的氨基糖苷耐药机制中，酶修饰在临床环境中最为普遍。氨基糖苷修饰酶催化2-脱氧链胺核或糖部分的不同- OH或- NH2基团的修饰，可以是核苷酸转移酶、磷酸转移酶或乙酰转移酶。迄今为止鉴定出的氨基糖苷修饰酶的数量以及编码基因所在的遗传环境令人印象深刻，几乎没有细菌不能支持酶对氨基糖苷的抗性。除了开发对尽可能多的修饰酶具有抗性的新氨基糖苷外，目前有两种主要的策略来克服氨基糖苷修饰酶的作用。它们的成功开发将延长已被证明在治疗感染方面有效的现有抗生素的使用寿命。这些策略包括开发抑制酶的作用或修饰酶的表达。
Aminoglycosides have been an essential component of the armamentarium in the treatment of life-threatening infections. Unfortunately, their efficacy has been reduced by the surge and dissemination of resistance. In some cases the levels of resistance reached the point that rendered them virtually useless. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevalent in the clinical setting. Aminoglycoside modifying enzymes catalyze the modification at different −OH or −NH2 groups of the 2-deoxystreptamine nucleus or the sugar moieties and can be nucleotidyltranferases, phosphotransferases, or acetyltransferases. The number of aminoglycoside modifying enzymes identified to date as well as the genetic environments where the coding genes are located is impressive and there is virtually no bacteria that is unable to support enzymatic resistance to aminoglycosides. Aside from the development of new aminoglycosides refractory to as many as possible modifying enzymes there are currently two main strategies being pursued to overcome the action of aminoglycoside modifying enzymes. Their successful development would extend the useful life of existing antibiotics that have proven effective in the treatment of infections. These strategies consist of the development of inhibitors of the enzymatic action or of the expression of the modifying enzymes.
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