Ahmad Zulfiqar, Hassan Sherif S, Azim Sofiya
Department of Biochemistry, Kirksville College of Osteopathic Medicine, A.T. Still University, Kirksville, Missouri 63501, USA.
Department of Medical Education, California University of Sciences and Medicine, School of Medicine (Cal Med-SOM), Colton, California 92324, USA.
Curr Med Chem. 2017 Nov 20;24(35):3894-3906. doi: 10.2174/0929867324666170823125330.
For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections.
几个世纪以来，植物化学物质一直被用于预防和治疗多种健康疾病。据报道，植物化学物质具有抗氧化、抗糖尿病、止咳、抗寄生虫、抗癌和抗菌特性。一般来说，植物化学物质的治疗用途基于传统或口口相传，几乎没有循证研究。此外，大多数植物化学物质的分子水平相互作用或分子靶点尚不清楚。近年来，微生物的抗生素耐药性已成为主要的医疗保健问题。因此，使用具有抗菌特性的植物化学物质变得至关重要。来自植物、蔬菜、草药和香料的具有强大抗菌特性的天然化合物为预防和对抗抗生素耐药性微生物感染提供了绝佳机会。ATP合酶是细胞能量的基本来源。抑制ATP合酶可能会使细胞失去所需能量，导致细胞死亡，并且已知多种膳食植物化学物质会抑制ATP合酶。植物化学物质的结构修饰已显示可提高抑制效力和抑制程度。定点诱变分析已阐明了一些植物化学物质在ATP合酶上的结合位点。植物化学物质结合位点及其周围的氨基酸变异可导致对微生物ATP合酶的选择性结合和抑制。在本综述中，基于膳食植物化学物质对ATP合酶的抑制作用，总结了膳食植物化学物质与ATP合酶之间的治疗联系。研究表明，选择性靶向ATP合酶是对抗抗生素耐药性微生物感染的一种有价值的替代分子水平方法。
