Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China.
Guangdong Ocean Engineering Technology School, Guangzhou, 510320, China.
Ecotoxicol Environ Saf. 2020 Jan 30;188:109910. doi: 10.1016/j.ecoenv.2019.109910. Epub 2019 Nov 15.
To alleviate the harmful effects of antibiotics on the environment and human health, the stress response and molecular network of Bacillus under tetracycline stress were investigated using a proteomics approach. During the exposure process, Bacillus subtilis exhibited a strong adaptation mechanism. Cell membrane and intracellular reactive oxygen species (ROS) level returned to normal after 5 h. A total of 312 upregulated and 65 downregulated proteins were identified, mainly involved in metabolism and the synthesis of ribosomes, DNA, and RNA. After tetracycline exposure, the core metabolism network was accelerated to supply precursors for the synthesis of DNA, RNA, proteins, peptidoglycans, and saturated fatty acids that were involved in ribosome protection, and strengthened the cell wall and cell membrane. The signal transduction pathways involved were analyzed in association with the stress response of B. subtilis at 15 min of exposure to tetracycline. The primary damage to the ribosome by tetracycline activated a series of response proteins. Antitoxin and heat-shock proteins were activated for the global regulation of transcription and metabolism. Trigger factor Tig was upregulated to ensure proper initiation of transcription and aerobic respiration. Temperature-sensor protein VicR from the two-component system was used by the cell to regulate the composition of the cell wall and cell membrane. The over-consumption of metabolites, such as phosphoribosyl diphosphate (PRPP), purine nucleoside triphosphate (GTP), and acetyl-CoA forced the cells to assimilate more sugar for glycolysis. To this end, methyl-accepting chemotaxis proteins (MCPs) and sugar transportation protein PtsG were upregulated, simultaneously. Ultimately, peroxidase was activated to eliminate the redundant ROS, to minimize cell damage. These findings presented a system-level understanding of adaption processes of bacteria to antibiotic stress.
为了减轻抗生素对环境和人类健康的有害影响，采用蛋白质组学方法研究了四环素胁迫下芽孢杆菌的应激反应和分子网络。在暴露过程中，枯草芽孢杆菌表现出很强的适应机制。细胞膜和细胞内活性氧（ROS）水平在 5 小时后恢复正常。共鉴定出 312 个上调蛋白和 65 个下调蛋白，主要涉及代谢和核糖体、DNA 和 RNA 的合成。四环素暴露后，核心代谢网络加速，为 DNA、RNA、蛋白质、肽聚糖和饱和脂肪酸的合成提供前体，这些物质参与核糖体保护，并加强细胞壁和细胞膜。分析了与枯草芽孢杆菌暴露于四环素 15 分钟时的应激反应相关的信号转导途径。四环素对核糖体的初步损伤激活了一系列反应蛋白。抗毒素和热休克蛋白被激活，以实现转录和代谢的全局调控。触发因子 Tig 被上调，以确保转录和需氧呼吸的适当起始。来自双组分系统的温度传感器蛋白 VicR 被细胞用来调节细胞壁和细胞膜的组成。代谢物（如磷酸核糖基二磷酸（PRPP）、嘌呤核苷三磷酸（GTP）和乙酰辅酶 A）的过度消耗迫使细胞消耗更多的糖进行糖酵解。为此，上调了甲基接受趋化蛋白（MCPs）和糖转运蛋白 PtsG。最终，激活过氧化物酶以消除多余的 ROS，最大限度地减少细胞损伤。这些发现提供了细菌对抗生素应激适应过程的系统理解。
