State Key Laboratory of Chemical Biology and Drug Discovery and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Chem Biol Interact. 2020 Apr 1;320:109023. doi: 10.1016/j.cbi.2020.109023. Epub 2020 Feb 22.
Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O), superoxide anion (O), hydrogen peroxide (HO) and hydroxyl radicals (OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.
抗菌药物耐药性仍然是一个严重的问题，导致全球死亡率升高和医疗保健费用增加。其中一个主要问题是，耐药病原体降低了常规抗菌药物的疗效。因此，迫切需要开发新型抗菌药物和治疗策略，以克服抗菌药物耐药性的挑战。一种潜在的策略是通过形成活性氧物种（ROS）来杀死致病微生物。ROS 被定义为由分子氧（O）、超氧阴离子（O）、过氧化氢（HO）和羟基自由基（OH）组成的许多高反应性分子。ROS 通过诱导氧化应激对广泛的病原体发挥抗菌作用，氧化应激是 ROS 与抗氧化防御系统清除 ROS 的能力之间的失衡。ROS 依赖性氧化应激可破坏细胞大分子，包括 DNA、脂质和蛋白质。本文综述了 ROS 的抗菌作用、ROS 假说面临的挑战、为巩固 ROS 介导的抗菌致死性假说所做的工作、利用 ROS 作为抗菌策略的新型抗菌药物的最新进展、与 ROS 相关的安全问题以及 ROS 研究的未来方向。
