Bloch Sylwia, Nejman-Faleńczyk Bożena, Pierzynowska Karolina, Piotrowska Ewa, Węgrzyn Alicja, Marminon Christelle, Bouaziz Zouhair, Nebois Pascal, Jose Joachim, Le Borgne Marc, Saso Luciano, Węgrzyn Grzegorz
a Department of Molecular Biology , Faculty of Biology, University of Gdansk , Gdansk , Poland.
b Laboratory of Molecular Biology , Institute of Biochemistry and Biophysics, Polish Academy of Sciences , Gdańsk , Poland.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):639-650. doi: 10.1080/14756366.2018.1444610.
Oxidative stress may be the major cause of induction of Shiga toxin-converting (Stx) prophages from chromosomes of Shiga toxin-producing Escherichia coli (STEC) in human intestine. Thus, we aimed to test a series of novel antioxidant compounds for their activities against prophage induction, thus, preventing pathogenicity of STEC. Forty-six compounds (derivatives of carbazole, indazole, triazole, quinolone, ninhydrine, and indenoindole) were tested. Fifteen of them gave promising results and were further characterized. Eleven compounds had acceptable profiles in cytotoxicity tests with human HEK-293 and HDFa cell lines. Three of them (selected for molecular studies) prevent the prophage induction at the level of expression of specific phage genes. In bacterial cells treated with hydrogen peroxide, expression of genes involved in the oxidative stress response was significantly less efficient in the presence of the tested compounds. Therefore, they apparently reduce the oxidative stress, which prevents induction of Stx prophage in E. coli.
氧化应激可能是人类肠道中志贺毒素产生大肠杆菌（STEC）染色体上志贺毒素转化（Stx）原噬菌体诱导的主要原因。因此，我们旨在测试一系列新型抗氧化化合物对原噬菌体诱导的活性，从而预防STEC的致病性。测试了46种化合物（咔唑、吲唑、三唑、喹诺酮、茚三酮和茚并吲哚的衍生物）。其中15种给出了有前景的结果并进一步进行了表征。11种化合物在用人HEK - 293和HDFa细胞系进行的细胞毒性测试中具有可接受的概况。其中3种（被选用于分子研究）在特定噬菌体基因表达水平上阻止原噬菌体诱导。在用过氧化氢处理的细菌细胞中，在存在测试化合物的情况下，参与氧化应激反应的基因表达效率明显较低。因此，它们显然降低了氧化应激，从而防止大肠杆菌中Stx原噬菌体的诱导。
