Antibacterial Antifolates: From Development through Resistance to the Next Generation.
Antibacterial Antifolates: From Development through Resistance to the Next Generation.
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DOI：
10.1101/cshperspect.a028324
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发表时间：
2016-08-01
影响因子：
5.4
通讯作者：
Anderson AC
中科院分区：
文献类型：
--
作者：
Estrada A;Wright DL;Anderson AC
叶酸循环是细菌合成增殖所需的重要组成部分的关键代谢途径之一。以这个循环中的酶为靶点的治疗药物，如甲氧苄啶和磺胺甲恶唑，是一些最重要和持续使用的抗菌药物，用于治疗革兰氏阳性和革兰氏阴性病原体。与所有抗菌剂一样，耐药性的出现威胁着这些救命药物的继续临床使用。在本文中，我们描述和分析了临床观察到的耐药机制，并回顾了旨在克服耐药分子基础的新一代临床前化合物。
The folate cycle is one of the key metabolic pathways used by bacteria to synthesize vital building blocks required for proliferation. Therapeutic agents targeting enzymes in this cycle, such as trimethoprim and sulfamethoxazole, are among some of the most important and continually used antibacterials to treat both Gram-positive and Gram-negative pathogens. As with all antibacterial agents, the emergence of resistance threatens the continued clinical use of these life-saving drugs. In this article, we describe and analyze resistance mechanisms that have been clinically observed and review newer generations of preclinical compounds designed to overcome the molecular basis of the resistance.