抗生素的不合理使用甚至滥用,使得细菌耐药性问题日趋严重。如何解决这一难题是人类目前面临的一项巨大挑战。除开发新型抗菌药物之外,寻找新的方法以增强现有抗生素的杀菌效果也是一种切实可行的策略。近期的研究发现活性氧簇(Reactive oxygen species, ROS)在细菌耐药及抗生素杀菌方面均发挥重要作用。非致死浓度的抗生素作用下产生的ROS会通过影响MarR(Multiple antibiotic resistance repressor)-MarA (Multiple antibiotic resistance activator)激活药物外排泵,通过SoxR(Superoxide response transcriptional regulator)-SoxS(Superoxide response transcription factor)途径启动细菌应激保护机制以及通过促进SOS DNA损伤修复系统诱导耐药突变,从而促成抗生素耐药与耐受的形成。而致死浓度的抗生素作用产生的ROS则会参与抗生素杀菌并减少耐药菌产生。除与抗生素浓度有关外,ROS参与细菌耐药与抗生素杀菌过程还会受到一系列遗传调控因子(如MazEF、Cpx、SoxR和MarRAB)的影响,因此存在一定复杂性。本文综述了ROS在细菌耐药与抗生素杀菌方面的作用机制,以期为寻找新的方法以增强现有抗生素杀菌效果,解决抗生素耐药问题提供一定的借鉴和指导。
Misuse and overuse of antibiotics have led to serious resistance problems that pose a grave threat to human health. How to solve the increasing antibiotic resistance problem is a huge challenge. Besides the traditional strategy of developing novel antimicrobial agents, exploring ways to enhance the lethal activity of antibiotics currently available is another feasible approach to fight against resistance. Recent studies showed that ROS plays an important role in regulating both antibiotic resistance and antimicrobial lethality. ROS produced by sublethal levels of antibiotic induces antibiotic resistance through activating drug efflux pumps via MarR(Multiple antibiotic resistance repressor)-MarA(Multiple antibiotic resistance activator), triggers the protective function against stress via SoxR (Superoxide response transcriptional regulator)-SoxS (Superoxide response transcription factor), and promotes mutagenesis by induction of SOS system. On the contrary, ROS triggered by lethal levels of antibiotic promotes bacterial killing and suppresses resistance. In addition to the concentration of antibiotic, the role of ROS in mediating antimicrobial resistance and bacterial killing is also regulated by a series of genetic regulators (e.g. MazEF, Cpx, SoxR, MarRAB). Thus, how ROS contribute to antimicrobial resistance and bacterial killing is complex. In this review, we summarized the mechanism of ROS in regulating antibiotic resistance and antimicrobial lethality, which may provide references and guidance for finding new ways to enhance antimicrobial lethality of currently available antimicrobials and battling antibiotic resistance.
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