Chemical Faculty, Lomonosov Moscow State University, Lenin Hills 1/3, 119991 Moscow, Russia.
Int J Mol Sci. 2022 Aug 20;23(16):9400. doi: 10.3390/ijms23169400.
The effect of Bacitracin as an antibiotic acting against Gram-positive bacterial cells was evaluated in combination with hexahistidine-containing organophosphate hydrolase (His-OPH), possessing lactonase activity against various -acylhomoserine lactones produced by most Gram-negative bacteria as quorum-sensing molecules. The molecular docking technique was used to obtain in silico confirmation of possible interactions between molecules of His-OPH and Bacitracin as well as the absence of a significant influence of such interactions on the enzymatic catalysis. The in vitro experiments showed a sufficient catalytic efficiency of action of the His-OPH/Bacitracin combination as compared to the native enzyme. The notable improvement (up to 3.3 times) of antibacterial efficiency of Bacitracin was revealed in relation to Gram-negative bacteria when it was used in combination with His-OPH. For the first time, the action of the Bacitracin with and without His-OPH was shown to be effective against various yeast strains, and the presence of the enzyme increased the antibiotic effect up to 8.5 times. To estimate the role of the enzyme in the success of His-OPH/Bacitracin with yeast, in silico experiments (molecular docking) with various fungous lactone-containing molecules were undertaken, and the opportunity of their enzymatic hydrolysis by His-OPH was revealed in the presence and absence of Bacitracin.
评估了含有六组氨酸的有机磷水解酶（His-OPH）与杆菌肽作为抗生素对革兰氏阳性细菌细胞的协同作用，His-OPH 具有针对大多数革兰氏阴性菌产生的各种 - 酰高丝氨酸内酯（作为群体感应分子）的内酯酶活性。使用分子对接技术获得了 His-OPH 和杆菌肽之间可能相互作用的计算机模拟确认，以及这些相互作用对酶催化的影响不大。体外实验表明，与天然酶相比，His-OPH/杆菌肽组合的作用具有足够的催化效率。当与 His-OPH 一起使用时，杆菌肽对革兰氏阴性菌的抗菌效率显著提高（高达 3.3 倍）。首次表明，含有和不含有 His-OPH 的杆菌肽对各种酵母菌株均有效，并且该酶的存在将抗生素的效果提高了 8.5 倍。为了评估酶在 His-OPH/杆菌肽与酵母协同作用中的作用，对含有各种真菌内酯的分子进行了计算机模拟实验（分子对接），并在有无杆菌肽的情况下揭示了 His-OPH 对它们进行酶水解的机会。
