Department of Pharmacognosy and Herbal Medicines, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland.
Molecules. 2021 Dec 21;27(1):20. doi: 10.3390/molecules27010020.
is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of , the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting survivability and virulence.
是人类最常见的病原体之一，也是各种胃病的主要病因。作为严格反应的协调者，SpoT 蛋白似乎对 的生存能力至关重要，本文的主要目标是使用计算机模拟计算研究来寻找能够与 中的 SpoT 活性位点结合的植物化学化合物，并通过体外实验确认最活跃的候选化合物干扰这种细菌毒力的能力。在提交虚拟筛选程序的 791 种天然物质中，选择了 10 种进行进一步的体外检查。其中，薯蓣皂素表现出最有趣的参数（最低 MIC、静态条件下最高的抗生物膜活性以及相对较低的诱导形态向球菌转变的刺激作用）。因此，在最后一部分，我们通过一系列进一步的实验扩展了研究，并观察到薯蓣皂素能够显著减少生物通量产生的流动条件下 的生物膜形成，以及它能够增强三种常用抗生素（克拉霉素、甲硝唑和左氧氟沙星）的抗菌活性的增效作用。基于这些结果，我们认为薯蓣皂素可能是针对 生存能力和毒力的新治疗方法的一个有前途的候选物。
