Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Institut für Biologie/Mikrobiologie, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany.
Sci Rep. 2020 May 22;10(1):8503. doi: 10.1038/s41598-020-65107-9.
The nickel-dependent urease enzyme is responsible for the hydrolysis of urea to ammonia and carbon dioxide. A number of bacteria produce urease (ureolytic bacteria) and are associated with various infectious diseases and ammonia emissions from agriculture. We report the first comprehensive comparison of the inhibition of urease activity by compounds analysed under the same conditions. Thus, 71 commercially available compounds were screened for their anti-ureolytic properties against both the ureolytic bacterium Klebsiella pneumoniae and purified jack bean urease. Of the tested compounds, 30 showed more than 25% inhibition of the ureolytic activity of Klebsiella pneumoniae or jack bean urease, and among these, carbon disulfide, N-phenylmaleimide, diethylenetriaminepentaacetic acid, sodium pyrrolidinedithiocarbamate, 1,2,4-butanetricarboxylic acid, tannic acid, and gallic acid have not previously been reported to possess anti-ureolytic properties. The diverse effects of metal ion chelators on ureolysis were investigated using a cellular nickel uptake assay. Ethylenediaminetetraacetic acid (EDTA) and dimethylglyoxime (DMG) clearly reduced the nickel import and ureolytic activity of cells, oxalic acid stimulated nickel import but reduced the ureolytic activity of cells, 1,2,4-butanetricarboxylic acid strongly stimulated nickel import and slightly increased the ureolytic activity of cells, while L-cysteine had no effect on nickel import but efficiently reduced the ureolytic activity of cells.
镍依赖的脲酶负责将尿素水解为氨和二氧化碳。许多细菌产生脲酶（脲分解细菌），并与各种传染病和农业氨排放有关。我们报告了首次对在相同条件下分析的化合物抑制脲酶活性的全面比较。因此，对 71 种市售化合物进行了筛选，以研究它们对脲分解菌肺炎克雷伯菌和纯化的豇豆脲酶的抗脲酶特性。在所测试的化合物中，有 30 种对肺炎克雷伯菌或豇豆脲酶的脲酶活性的抑制作用超过 25%，其中，二硫化碳、N-苯马来酰亚胺、二亚乙基三胺五乙酸、吡啶二硫代羧酸、1,2,4-丁烷三羧酸、鞣酸和没食子酸以前没有报道过具有抗脲酶特性。使用细胞镍摄取测定法研究了金属离子螯合剂对脲解作用的不同影响。乙二胺四乙酸（EDTA）和二甲基乙二肟（DMG）明显降低了细胞的镍摄取和脲酶活性，草酸刺激了镍的摄取，但降低了细胞的脲酶活性，1,2,4-丁烷三羧酸强烈地刺激了镍的摄取，同时稍微增加了细胞的脲酶活性，而 L-半胱氨酸对镍摄取没有影响，但有效地降低了细胞的脲酶活性。
