Cabezón Elena, de la Cruz Fernando, Arechaga Ignacio
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria and Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Front Microbiol. 2017 Nov 30;8:2329. doi: 10.3389/fmicb.2017.02329. eCollection 2017.
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.
抗生素耐药性已成为医疗保健领域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,寻找特异性接合抑制剂(COINs)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。作为COINs发现的几种化合物是对抗质粒传播的有前景的候选物。在本综述中,我们调查了最相关化合物的有效性和毒性。特别强调了不饱和脂肪酸衍生物,因为它们已被证明在防止质粒在细菌群体中的侵袭性方面是有效的。生化和结构研究提供了有关其潜在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一条新途径。在这一探索过程中,基于结构的药物设计方法的使用对于筛选假定靶点的配体和结合位点将非常重要。