Molecular Metabolic Engineering Lab, Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Department of Biotechnology, Modern College of Arts, Science and Commerce, Savitribai Phule Pune University, Ganeshkhind, Pune 411016, India; Department of Environmental Science, Savitribai Phule Pune University, Pune 411007, India.
Biotechnol Adv. 2021 May-Jun;48:107729. doi: 10.1016/j.biotechadv.2021.107729. Epub 2021 Mar 9.
Inappropriate and injudicious use of antimicrobial drugs in human health, hygiene, agriculture, animal husbandry and food industries has contributed significantly to rapid emergence and persistence of antimicrobial resistance (AMR), one of the serious global public health threats. The crisis of AMR versus slower discovery of newer antibiotics put forth a daunting task to control these drug-resistant superbugs. Several phyto-antimicrobials have been identified in recent years with direct-killing (bactericidal) and/or drug-resistance reversal (re-sensitization of AMR phenotypes) potencies. Phyto-antimicrobials may hold the key in combating AMR owing to their abilities to target major microbial drug-resistance determinants including cell membrane, drug-efflux pumps, cell communication and biofilms. However, limited distribution, low intracellular concentrations, eco-geographical variations, beside other considerations like dynamic environments, climate change and over-exploitation of plant-resources are major blockades in full potential exploration phyto-antimicrobials. Synthetic biology (SynBio) strategies integrating metabolic engineering, RNA-interference, genome editing/engineering and/or systems biology approaches using plant chassis (as engineerable platforms) offer prospective tools for production of phyto-antimicrobials. With expanding SynBio toolkit, successful attempts towards introduction of entire gene cluster, reconstituting the metabolic pathway or transferring an entire metabolic (or synthetic) pathway into heterologous plant systems highlight the potential of this field. Through this perspective review, we are presenting herein the current situation and options for addressing AMR, emphasizing on the significance of phyto-antimicrobials in this apparently post-antibiotic era, and effective use of plant chassis for phyto-antimicrobial production at industrial scales along with major SynBio tools and useful databases. Current knowledge, recent success stories, associated challenges and prospects of translational success are also discussed.
在人类健康、卫生、农业、畜牧业和食品工业中不恰当地、不明智地使用抗菌药物，是导致抗菌药物耐药性（AMR）迅速出现和持续存在的主要原因之一，这是全球严重的公共卫生威胁之一。AMR 与新抗生素发现速度较慢的问题形成了巨大挑战，需要控制这些耐药性超级细菌。近年来，已经发现了几种植物抗菌药物，具有直接杀菌（杀菌）和/或耐药逆转（恢复 AMR 表型的敏感性）作用。由于植物抗菌药物能够靶向主要的微生物药物耐药决定因素，包括细胞膜、药物外排泵、细胞通讯和生物膜，因此可能是对抗 AMR 的关键。然而，分布有限、细胞内浓度低、生态地理变化，以及其他考虑因素，如动态环境、气候变化和过度开发植物资源，是充分挖掘植物抗菌药物潜力的主要障碍。整合代谢工程、RNA 干扰、基因组编辑/工程和/或系统生物学方法的合成生物学（SynBio）策略，使用植物底盘（可工程化平台），为植物抗菌药物的生产提供了有前景的工具。随着 SynBio 工具包的扩展，成功地尝试引入整个基因簇、重新构建代谢途径或将整个代谢（或合成）途径转移到异源植物系统中，突出了该领域的潜力。通过本次观点综述，我们介绍了目前应对 AMR 的情况和选择，强调了在这个明显的后抗生素时代植物抗菌药物的重要性，以及在工业规模上使用植物底盘进行植物抗菌药物生产的有效性，同时还介绍了主要的 SynBio 工具和有用的数据库。还讨论了当前的知识、最近的成功案例、相关挑战和转化成功的前景。
