Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.
Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.
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白藜芦醇拮抗抗菌剂的杀伤力并刺激细菌突变体的恢复。
DOI：
10.1371/journal.pone.0153023
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Liu Y;Zhou J;Qu Y;Yang X;Shi G;Wang X;Hong Y;Drlica K;Zhao X
活性氧物种(ROS；超氧化物、过氧化氢和羟基自由基)被认为有助于各种抗菌剂的快速杀菌活性。食品中抗氧化剂的摄入可能会干扰抗菌剂的致命作用，这一可能性已经被提出。含有抗氧化剂活性的营养补充剂是否也可能干扰抗微生物的致死性尚不清楚。为了检验这种可能性，在大肠杆菌和金黄色葡萄球菌的培养中加入了白藜芦醇，这是一种流行的抗氧化剂膳食补充剂，然后用抗菌剂处理这些培养物，并检测细菌存活率和对无关抗菌剂利福平的抗药性突变株的恢复情况。白藜芦醇的浓度可能存在于人类消费中，在与莫西沙星或卡那霉素治疗2小时期间，白藜芦醇导致的死亡人数减少了2-3倍。在更高的，但仍然是亚抑制浓度，白藜芦醇降低了3个数量级以上的抗菌剂致死率。白藜芦醇还减少了喹诺酮(恶唑酸)治疗所特有的活性氧簇(ROS)的增加。这些数据支持一些抗菌剂的致死活性与ROS有关的普遍观点。令人惊讶的是，低抑制浓度的白藜芦醇可促进(2-6倍)因环丙沙星、卡那霉素或达托霉素作用而产生的利福平耐药突变的恢复。这一结果与白藜芦醇将ROS降低到仍然具有致突变作用的亚致死水平是一致的，而没有白藜芦醇则允许ROS水平高到足以杀死诱变细胞。白藜芦醇抑制抗菌剂的杀伤力和促进突变体的恢复表明，抗氧化剂可能有助于出现对几种抗菌剂的耐药性，特别是如果白藜芦醇的新衍生物和/或制剂显著提高了生物利用度。
Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical) are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS) characteristic of treatment with quinolone (oxolinic acid). These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold) the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability.