Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, 13488, Republic of Korea.
J Microbiol. 2019 Mar;57(3):203-212. doi: 10.1007/s12275-019-8711-9. Epub 2019 Feb 26.
Oxidative stress arises from an imbalance between the excessive accumulation of reactive oxygen species (ROS) and a cell's capability to readily detoxify them. Although ROS are spontaneously generated during the normal oxygen respiration and metabolism, the ROS generation is usually augmented by redox-cycling agents, membrane disrupters, and bactericidal antibiotics, which contributes their antimicrobial bioactivity. It is noted that all the bacteria deploy an arsenal of inducible antioxidant defense systems to cope with the devastating effect exerted by the oxidative stress: these systems include the antioxidant effectors such as catalases and the master regulators such as OxyR. The oxidative stress response is not essential for normal growth, but critical to survive the oxidative stress conditions that the bacterial pathogens may encounter due to the host immune response and/or the antibiotic treatment. Based on these, we here define the ROS-inspired antibacterial strategies to enhance the oxidative stress of ROS generation and/or to compromise the bacterial response of ROS detoxification, by delineating the ROSgenerating antimicrobials and the core concept of the bacterial response against the oxidative stress.
氧化应激是由于活性氧(ROS)的过度积累和细胞清除它们的能力之间的失衡而产生的。虽然 ROS 在正常的氧气呼吸和代谢过程中会自发产生,但 ROS 的产生通常会被氧化还原循环剂、膜破坏剂和杀菌抗生素增强,这些物质有助于它们的抗菌生物活性。需要注意的是,所有细菌都部署了一系列可诱导的抗氧化防御系统来应对氧化应激的破坏性影响:这些系统包括过氧化氢酶等抗氧化效应物和 OxyR 等主要调节剂。氧化应激反应对于正常生长不是必需的,但对于细菌病原体因宿主免疫反应和/或抗生素治疗而可能遇到的氧化应激条件的生存至关重要。基于这些,我们在这里定义了受 ROS 启发的抗菌策略,通过描述产生 ROS 的抗菌剂和细菌对氧化应激的反应的核心概念,来增强 ROS 生成的氧化应激和/或损害细菌清除 ROS 的反应。