Shriram Varsha, Khare Tushar, Bhagwat Rohit, Shukla Ravi, Kumar Vinay
Department of Botany, Prof. Ramkrishna More College, Savitribai Phule Pune University, Pune, India.
Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University), Pune, India.
Front Microbiol. 2018 Dec 10;9:2990. doi: 10.3389/fmicb.2018.02990. eCollection 2018.
Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of tools, major success stories, challenges and future prospects are also discussed.
抗生素曾被视为治疗细菌感染的生命线，但由于具有威胁性的抗菌耐药性（AMR）的出现，正面临威胁。这些耐药微生物（或超级细菌）对大多数常用抗生素无反应，留给我们的治疗选择很少，且死亡率和治疗成本不断攀升。新的强效抗生素研发管道枯竭，尤其是对耐药菌株有效的抗生素，这一问题进一步恶化。多药外排泵（EPs）已被确认为AMR的主要决定因素，能将多种抗生素排出细胞外，大多以非特异性方式，因此已成为对抗AMR的有效药物靶点。植物作为生物活性化合物的储存库，可作为强效EP抑制剂（EPIs）的来源。具有显著耐药性逆转或重新致敏活性的植物疗法，可能对重振日渐式微的抗生素库并使这种联合疗法有效具有重要意义。目前用植物提取物和纯植物分子增强抗生素效果的尝试虽有进展，但对革兰氏阴性菌的效果相对较差。基于植物的EPIs有望成为对抗EPI介导的AMR的有效药物先导。本综述介绍了主要的细菌多药EPs及其在赋予AMR中的作用、用植物分子抑制药物EPs的有效策略，以及目前开发新型强效植物基EPIs以逆转其AMR特性的研究情况。还讨论了包括工具出现、主要成功案例、挑战和未来前景在内的最新进展。
