Laboratory of Microbial Adaptation, Institute of Ecology and Genetics of Microorganisms UB RAS, 13 Golev str., Perm 614081, Russia.
Res Microbiol. 2012 Feb;163(2):83-91. doi: 10.1016/j.resmic.2011.10.009. Epub 2011 Nov 16.
Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins) at their sublethal concentrations were able to produce hydroxyl radicals, hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which resulted in damage to proteins and DNA. The cells responded to oxidative stress by a 2-3-fold increase in cell polyamines (putrescine, spermidine) produced as a consequence of upregulation of ornithine decarboxylase (ODC). Relief of oxidative stress by cessation of culture aeration or addition of antioxidants substantially diminished or even completely abolished polyamine accumulation observed in response to antibiotics. Alternatively, inhibition of polyamine synthesis resulted in enhancement of oxidative stress in antibiotic-processed cells. When added to antibiotic-inhibited culture, polyamines reduced intracellular ROS production and thereby prevented damage to proteins and DNA. These effects eventually resulted in a substantial increase in cell viability, growth recovery and antibiotic resistance that were more strongly expressed in polyamine-deficient mutants.
在亚致死浓度下,杀菌抗生素(氟喹诺酮类、氨基糖苷类和头孢菌素类)能够在大肠杆菌细胞中产生羟基自由基、过氧化氢和超氧阴离子(ROS),导致蛋白质和 DNA 受损。细胞通过增加细胞多胺(腐胺、亚精胺)的产生来应对氧化应激,这是由于鸟氨酸脱羧酶(ODC)的上调所致。停止培养通气或添加抗氧化剂来缓解氧化应激,可大大减少甚至完全消除抗生素处理细胞中观察到的多胺积累。相反,抑制多胺合成会导致抗生素处理细胞中的氧化应激增强。当添加到被抗生素抑制的培养物中时,多胺会减少细胞内 ROS 的产生,从而防止蛋白质和 DNA 受损。这些作用最终导致细胞活力、生长恢复和抗生素耐药性的显著增加,在多胺缺乏突变体中表达得更为强烈。