Liu Wei, Chen Guang, Dou Keke, Yi Bingcheng, Wang Danyang, Zhou Qihui, Sun Yunbo
Department of Critical Care Medicine, College of Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Institute for Translational Medicine, Qingdao, China.
Front Microbiol. 2023 Feb 16;14:1090787. doi: 10.3389/fmicb.2023.1090787. eCollection 2023.
Multidrug-resistant (MDR) bacterial infections have gained increasing attention due to the high incidence rates and high mortality, especially for the carbapenem-resistant (CRKP) infection that can cause severe complications (e.g., pneumonia and sepsis) in multiple organs. Therefore, the development of new antibacterial agents against CRKP is imperative. Inspired by natural plant antibacterial agents with broad-spectrum antibacterial properties, the antibacterial/biofilm activity of eugenol (EG) on CRKP and their underlying mechanisms are investigated in our work. It is found that EG exhibits remarkable inhibitory effects on planktonic CRKP in a dose-dependent fashion. Meanwhile, the destruction of membrane integrity induced by the formation of reactive oxygen species (ROS) and glutathione reduction results in the leakage of bacterial cytoplasmic components, including DNA, β-galactosidase, and protein. Moreover, when EG contacts with bacterial biofilm, the whole thickness of the dense biofilm matrix decreases, and the integrity is destroyed. Overall, this work verified that EG could eliminate CRKP ROS-induced membrane rupture, which offers vital evidence to explain the antibacterial ability of EG against CRKP.
多重耐药（MDR）细菌感染因其高发病率和高死亡率而日益受到关注，尤其是耐碳青霉烯类肺炎克雷伯菌（CRKP）感染，它可在多个器官引发严重并发症（如肺炎和败血症）。因此，开发针对CRKP的新型抗菌剂势在必行。受具有广谱抗菌特性的天然植物抗菌剂启发，我们的研究工作考察了丁香酚（EG）对CRKP的抗菌/生物膜活性及其潜在机制。研究发现，EG对浮游CRKP呈现出显著的剂量依赖性抑制作用。同时，活性氧（ROS）形成和谷胱甘肽还原诱导的膜完整性破坏导致细菌细胞质成分（包括DNA、β-半乳糖苷酶和蛋白质）泄漏。此外，当EG与细菌生物膜接触时，致密生物膜基质的整体厚度减小，完整性遭到破坏。总体而言，这项工作证实EG可通过ROS诱导的膜破裂消除CRKP，这为解释EG对CRKP的抗菌能力提供了重要证据。
