Biomedical Sciences Program, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Biology Program, Faculty of Science and Technology, Pibulsongkram Rajabhat University, Phitsanulok 65000, Thailand.
Int J Mol Sci. 2023 Sep 10;24(18):13914. doi: 10.3390/ijms241813914.
Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlying mechanism of action. Here, we aimed to investigate the antibacterial effect of hydroquinine in clinical strains using phenotypic antimicrobial susceptibility testing and synergistic testing. In addition, we examined the potential inhibitory mechanisms against MDR isolates using informatic-driven molecular docking analysis in combination with RT-qPCR. We uncovered that hydroquinine inhibits and kills clinical at 2.50 mg/mL (MIC) and 5.00 mg/mL (MBC), respectively. Hydroquinine also showed partial synergistic effects with ceftazidime against clinical MDR strains. Using SwissDock, we identified potential interactions between arginine deiminase (ADI)-pathway-related proteins and hydroquinine. Furthermore, using RT-qPCR, we found that hydroquinine directly affects the mRNA expression of operon. We demonstrated that the ADI-related genes, including the arginine/ornithine antiporter () and the three enzymes (arginine deiminase (), ornithine transcarbamylase (), and carbamate kinase ()), were significantly downregulated at a half MIC of hydroquinine. This study is the first report that the ADI-related proteins are potential molecular targets for the inhibitory effect of hydroquinine against clinically isolated MDR strains.
氢奎宁具有抗菌潜力，已证明对多种细菌具有活性，包括多药耐药（MDR）参考菌株。尽管如此，证实氢奎宁对临床分离株的抗菌活性及其潜在作用机制的证据有限。在这里，我们旨在使用表型抗菌药敏试验和协同试验来研究氢奎宁在临床菌株中的抗菌作用。此外，我们还使用信息驱动的分子对接分析结合 RT-qPCR 检查了针对 MDR 分离株的潜在抑制机制。我们发现氢奎宁分别在 2.50 mg/mL（MIC）和 5.00 mg/mL（MBC）时抑制和杀死临床分离株。氢奎宁与头孢他啶联合使用时对临床 MDR 菌株也显示出部分协同作用。使用 SwissDock，我们确定了与精氨酸脱亚氨酶（ADI）途径相关蛋白和氢奎宁之间潜在的相互作用。此外，通过 RT-qPCR，我们发现氢奎宁直接影响操纵子的 mRNA 表达。我们证明，ADI 相关基因，包括精氨酸/鸟氨酸反向转运蛋白（）和三种酶（精氨酸脱氨酶（）、鸟氨酸转氨甲酰酶（）和氨基甲酰激酶（）），在氢奎宁的半 MIC 时显着下调。这项研究是第一个报告 ADI 相关蛋白是氢奎宁抑制临床分离的 MDR 菌株的潜在分子靶标。
