Conjugation Inhibitors and Their Potential Use to Prevent Dissemination of Antibiotic Resistance Genes in Bacteria.
Conjugation Inhibitors and Their Potential Use to Prevent Dissemination of Antibiotic Resistance Genes in Bacteria.
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DOI：
10.3389/fmicb.2017.02329
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发表时间：
2017
影响因子：
5.2
通讯作者：
Arechaga I
中科院分区：
文献类型：
--
作者：
Cabezón E;de la Cruz F;Arechaga I
抗生素耐药性已成为卫生保健中最具挑战性的问题之一。细菌接合是细菌对抗生素产生耐药性的主要机制之一。因此，寻找特异性缀合抑制剂（COIN）对于在各种实验室和自然环境中对抗抗生素耐药性的传播具有重要意义。几种化合物，被发现为COIN，是对抗质粒传播的有希望的候选者。在这篇综述中，我们调查了最相关的化合物的有效性和毒性。特别强调的是不饱和脂肪酸衍生物，因为它们已被证明是有效的，在防止质粒侵入细菌种群。生物化学和结构研究提供了关于其潜在的分子靶点和抑制机制的见解。这些发现为寻找新的更有效的合成抑制剂开辟了新的途径。在这方面，基于结构的药物设计方法的使用将是非常重要的配体和潜在靶点的结合位点的筛选。
Antibiotic resistance has become one of the most challenging problems in health care. Bacteria conjugation is one of the main mechanisms whereby bacteria become resistant to antibiotics. Therefore, the search for specific conjugation inhibitors (COINs) is of interest in the fight against the spread of antibiotic resistances in a variety of laboratory and natural environments. Several compounds, discovered as COINs, are promising candidates in the fight against plasmid dissemination. In this review, we survey the effectiveness and toxicity of the most relevant compounds. Particular emphasis has been placed on unsaturated fatty acid derivatives, as they have been shown to be efficient in preventing plasmid invasiveness in bacterial populations. Biochemical and structural studies have provided insights concerning their potential molecular targets and inhibitory mechanisms. These findings open a new avenue in the search of new and more effective synthetic inhibitors. In this pursuit, the use of structure-based drug design methods will be of great importance for the screening of ligands and binding sites of putative targets.