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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Suppression of Reactive Oxygen Species Accumulation Accounts for Paradoxical Bacterial Survival at High Quinolone Concentration
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Suppression of Reactive Oxygen Species Accumulation Accounts for Paradoxical Bacterial Survival at High Quinolone Concentration

机译：抑制反应性氧物种的累积占高喹啉浓度下矛盾的细菌存活率

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摘要

When bacterial cells are exposed to increasing concentrations of quinolone-class antibacterials, survival drops, reaches a minimum, and then recovers, sometimes to 100%. Despite decades of study, events underlying this paradoxical high-concentration survival remain obscure. Since reactive oxygen species (ROS) have been implicated in antimicrobial lethality, conditions generating paradoxical survival were examined for diminished ROS accumulation. Escherichia coli cultures were treated with various concentrations of nalidixic acid, followed by measurements of survival, rate of protein synthesis, and ROS accumulation. The last measurement used a dye (carboxy-H2DCFDA) that fluoresces in the presence of ROS; fluorescence was assessed by microscopy (individual cells) and flow cytometry (batch cultures). High, nonlethal concentrations of nalidixic acid induced lower levels of ROS than moderate, lethal concentrations. Sublethal doses of exogenous hydrogen peroxide became lethal and eliminated the nalidixic acid-associated paradoxical survival. Thus, quinolone-mediated lesions needed for ROS-executed killing persist at high, nonlethal quinolone concentrations, thereby implicating ROS as a key factor in cell death. Chloramphenicol suppressed nalidixic acid-induced ROS accumulation and blocked lethality, further supporting a role for ROS in killing. Nalidixic acid also inhibited protein synthesis, with extensive inhibition at high concentrations correlating with lower ROS accumulation and paradoxical survival. A catalase deficiency, which elevated ROS levels, overcame the inhibitory effect of chloramphenicol on nalidixic acid-mediated killing, emphasizing the importance of ROS. The data collectively indicate that ROS play a dominant role in the lethal action of narrow-spectrum quinolone-class compounds; a drop in ROS levels accounted for the quinolone tolerance observed at very high concentrations.
机译：当细菌细胞暴露于喹耳类抗菌浓度的增加时，存活下降，达到最小，然后恢复，有时达到100％。尽管几十年的研究，这种矛盾的高浓度存活率的事件仍然模糊不清。由于反应性氧物质（ROS）与抗微生物致死致死，因此检查了产生矛盾存活的条件，以减少ROS积累。大肠杆菌培养物用各种浓度的萘啶酸处理，然后测量存活，蛋白质合成率和ROS积累。最后一次测量用染料（羧基-H2DCFDA）在ROS存在下荧光;通过显微镜（个体细胞）和流式细胞术（分批培养物）评估荧光。高，非致密的硝酸浓度诱导较低水平的ROS，而不是中等的致死浓度。亚致致死剂量的外源性过氧化氢成为致命的，消除了脱硫酸相关的矛盾存活。因此，ROS执行的杀灭杀死所需的喹诺酮介导的病变在高度不静脉喹啉浓度下持续存在，从而将ROS视为细胞死亡的关键因素。氯霉素抑制了脱硫酸诱导的ROS积累并阻断了致命性，进一步支持杀死ROS的作用。萘啶酸还抑制蛋白质合成，在高浓度下具有广泛的抑制，与较低的ROS积累和矛盾的存活率相关。过氧化氢酶缺乏率升高的ROS水平，克服氯霉素对脱硫酸介导的杀伤的抑制作用，强调ROS的重要性。这些数据共同表明ROS在窄光谱喹啉类化合物的致命作用中发挥着主导作用; ROS水平下降占在非常高浓度观察到的喹诺酮耐受性。

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