Reduced ROS-mediated antibiotic resistance and its reverting by glucose in Vibrio alginolyticus
Reduced ROS-mediated antibiotic resistance and its reverting by glucose in Vibrio alginolyticus
复制标题
溶藻弧菌中 ROS 介导的抗生素耐药性降低及其通过葡萄糖的恢复
DOI：
10.1111/1462-2920.15085
复制
发表时间：
2020-06-08
影响因子：
5.1
通讯作者：
Li, Hui
中科院分区：
文献类型：
--
作者：
Zhang, Song;Yang, Man-Jun;Li, Hui
耐药溶藻弧菌对人类健康和食品安全构成了巨大挑战。因此，迫切需要了解抗生素耐药性的机制，以开发有效的控制方法。在这里，我们探讨了庆大霉素耐药溶藻弧菌（VA-R-GEN）和庆大霉素敏感溶藻弧菌（VA-S）之间的代谢差异，并发现活性氧（ROS）的产生发生了改变。与VA-S相比，VA-R-GEN中活性氧的产生减少，分解增加，从而降低了活性氧的含量。ROS产生的减少归因于中心碳代谢的减少，这与庆大霉素的耐药性有关。因此，我们认为外源性葡萄糖刺激VA-R-GEN，激活中心碳代谢，促进ROS的产生，但降低了VA-R-GEN中ROS的分解，并通过葡萄糖与庆大霉素的协同作用，使庆大霉素的杀伤作用随着ROS水平的升高而增强。活性氧清除剂硫脲可抑制协同效应。这些结果揭示了ROS介导的抗生素耐药性机制的降低及其被外源性葡萄糖逆转。
Antibiotic-resistant Vibrio alginolyticus poses a big challenge to human health and food safety. It is urgently needed to understand the mechanisms underlying antibiotic resistance to develop effective approaches for the control. Here we explored the metabolic difference between gentamicin-resistant V. alginolyticus (VA-R-GEN) and gentamicin-sensitive V. alginolyticus (VA-S), and found that the reactive oxygen species (ROS) generation was altered. Compared with VA-S, the ROS content in VA-R-GEN was reduced due to the decreased generation and increased breakdown of ROS. The decreased production of ROS was attributed to the decreased central carbon metabolism, which is associated with the resistance to gentamicin. As such a mechanism, we exogenously administrated VA-R-GEN with the glucose that activated the central carbon metabolism and promoted the generation of ROS, but decreased the breakdown of ROS in VA-R-GEN. The gentamicin-mediated killing was increased with the elevation of the ROS level by a synergistic effect between gentamicin and exogenous glucose. The synergistic effect was inhibited by thiourea, a scavenger of ROS. These results reveal a reduced ROS-mediated antibiotic resistance mechanism and its reversal by exogenous glucose.