MicroLife Solutions B.V., Science Park 406, 1098 XH Amsterdam, the Netherlands.
National Institute for Public Health and the Environment (RIVM), Centre for Infectious Diseases, Epidemiology and Surveillance, Endemic and Emerging Viruses section, Antonie van Leeuwenhoeklaan 9, 37221 MA Bilthoven, the Netherlands.
FEMS Microbiol Lett. 2019 Feb 1;366(3). doi: 10.1093/femsle/fnz023.
Pyrazines are 1,4-diazabenzene-based volatile organic compounds and known for their broad-spectrum antimicrobial activity. In the present study, we assessed the antimicrobial activity of 2,5-bis(1-methylethyl)-pyrazine, produced by Paenibacillus sp. AD87 during co-culture with Burkholderia sp. AD24. In addition, we were using transcriptional reporter assays in E. coli and mammalian cells to decipher the possible mode of action. Bacterial and mammalian luciferase reporter strains were deployed to elucidate antimicrobial and toxicological effects of 2,5-bis(1-methylethyl)-pyrazine. At high levels of exposure, 2,5-bis(1-methylethyl)-pyrazine exerted strong DNA damage response. At lower concentrations, cell-wall damage response was observed. The activity was corroborated by a general toxicity reporter assay in E. coli ΔampD, defective in peptidoglycan turnover. The maximum E. coli cell-wall stress activity was measured at a concentration close to the onset of the mammalian cytotoxicity, while other adverse outcome pathways, such as the activation of aryl hydrocarbon and estrogenic receptor, the p53 tumour suppressor and the oxidative stress-related Nrf2 transcription factor, were induced at elevated concentrations compared to the response of mammalian cells. Because of its broad-spectrum antimicrobial activity at lower concentrations and the relatively low mammalian toxicity, 2,5-bis(1-methylethyl)-pyrazine is a potential bio-based fumigant with possible applications in food industry, agriculture or logistics.
吡嗪是一种基于 1,4-二氮杂苯的挥发性有机化合物，以其广谱的抗菌活性而闻名。在本研究中，我们评估了由 Paenibacillus sp. AD87 在与 Burkholderia sp. AD24 共培养时产生的 2,5-双(1-甲基乙基)-吡嗪的抗菌活性。此外，我们还使用转录报告基因检测在大肠杆菌和哺乳动物细胞中破译可能的作用模式。我们使用细菌和哺乳动物荧光素酶报告株来阐明 2,5-双(1-甲基乙基)-吡嗪的抗菌和毒理学效应。在高暴露水平下，2,5-双(1-甲基乙基)-吡嗪会引发强烈的 DNA 损伤反应。在较低浓度下，会观察到细胞壁损伤反应。大肠杆菌 ΔampD 的一般毒性报告基因检测实验证实了该活性，该突变株在肽聚糖周转中存在缺陷。在接近哺乳动物细胞毒性的起始浓度时，大肠杆菌细胞壁应激活性达到最大值，而其他不良结局途径，如芳基烃和雌激素受体的激活、p53 肿瘤抑制因子和与氧化应激相关的 Nrf2 转录因子的激活，则在高于哺乳动物细胞响应的浓度下被诱导。由于其在较低浓度下具有广谱抗菌活性和相对较低的哺乳动物毒性，2,5-双(1-甲基乙基)-吡嗪是一种有潜力的生物基熏蒸剂，可能在食品工业、农业或物流领域得到应用。
