Environmental Biotechnology Laboratory, Centre for Rural Development and Technology, Indian Institute of Technology Delhi, Delhi 110016, India.
Environmental Biotechnology Laboratory, Centre for Rural Development and Technology, Indian Institute of Technology Delhi, Delhi 110016, India.
Fitoterapia. 2020 Nov;147:104762. doi: 10.1016/j.fitote.2020.104762. Epub 2020 Oct 16.
Development of antibiotic resistance (ABR) in bacteria and its multidimensional spread is an emerging global threat that needs immediate attention. Extensive antibiotics (AB) usage results in development of ABR in bacteria by target modification, production of AB degrading enzymes, porin modifications, efflux pumps overexpression, etc. To counter this, apart from strict regulation of AB use and behavioural changes, research and development (R&D) of newer antimicrobials are in place. One such emerging approach to combat ABR is the use of structurally and functionally diverse plant secondary metabolites (PSMs) in combination with the conventional AB. Either the PSMs are themselves antimicrobial or they potentiate the activity of the AB through a range of mechanisms. However, their use is lagging due to poor knowledge of mode of action, structure-activity relationships, pharmacokinetics, etc. This review paper discussed the opportunities and challenges in managing ABR using PSMs. Mechanisms of ABR development in bacteria and current strategies to counter them were studied and the areas where PSMs can play an important role were highlighted. The use of PSMs, both as an anti-resistance and anti-virulence agent in combination therapy to counter multi-drug resistance along with their mechanisms of action, has been discussed in detail. The difficulties in the commercialisation of PSMs and strategies to overcome them along with future priority areas of research have also been given. Following the given R&D path will definitely help in better understanding and utilising the full potential of PSMs in solving the problem of antimicrobial resistance (AMR).
细菌对抗生素耐药性（ABR）的发展及其多维度传播是一个新出现的全球威胁，需要立即引起关注。广泛使用抗生素（AB）会导致细菌通过靶标修饰、产生 AB 降解酶、孔蛋白修饰、外排泵过度表达等方式产生 ABR。为了应对这一问题，除了严格规范 AB 的使用和行为改变外，还在进行新的抗菌药物的研究和开发（R&D）。一种新兴的对抗 ABR 的方法是将结构和功能多样化的植物次生代谢物（PSMs）与传统 AB 联合使用。这些 PSMs 本身具有抗菌作用，或者通过一系列机制增强 AB 的活性。然而，由于对作用机制、构效关系、药代动力学等了解不足，它们的应用滞后。本文综述了使用 PSMs 管理 ABR 的机会和挑战。研究了细菌中 ABR 发展的机制和当前对抗它们的策略，并强调了 PSMs 可以发挥重要作用的领域。详细讨论了 PSMs 作为联合治疗中的抗耐药性和抗毒力剂的用途及其作用机制。还讨论了 PSMs 商业化的困难以及克服这些困难的策略，以及未来的研究重点领域。遵循既定的研发路径肯定有助于更好地理解和利用 PSMs 的全部潜力，以解决抗菌药物耐药性（AMR）问题。
