Duda-Madej Anna, Viscardi Szymon, Niezgódka Piotr, Szewczyk Wiktoria, Wińska Katarzyna
Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Chałubińskiego 4, 50-368 Wrocław, Poland.
Faculty of Medicine, Wroclaw Medical University, Ludwika Pasteura 1, 50-367 Wrocław, Poland.
Int J Mol Sci. 2025 Apr 24;26(9):4030. doi: 10.3390/ijms26094030.
The global healthcare system is increasingly challenged by the rising prevalence of multidrug-resistant bacteria and the limited therapeutic options for related infections. Efflux-mediated antibiotic resistance represents a significant obstacle, primarily due to the absence of drugs specifically designed to target bacterial efflux pumps. Recent research has identified polyphenols, a broad class of plant-derived organic compounds, as potential inhibitors of efflux pump activity. This review consolidates data on the inhibitory properties of eight widely distributed polyphenols: curcumin, quercetin, luteolin, tannic acid, naringenin, epigallocatechin-3-gallate, ellagic acid, and resveratrol. These compounds have demonstrated the capacity to inhibit efflux pumps, either through direct interference with bacterial protein function or by downregulating the expression of genes encoding pump subunits. Importantly, several polyphenols exhibit synergistic interactions with antibiotics, including colistin, ciprofloxacin, and tetracycline. For instance, quercetin has shown inhibitory potency comparable to that of established efflux pump inhibitors such as verapamil and reserpine. These findings suggest that polyphenols represent promising candidates for the development of novel efflux pump inhibitors. However, further research is required to validate their efficacy and safety and facilitate their translation into clinical applications for combating antibiotic resistance.
全球医疗保健系统正日益受到多重耐药菌患病率上升以及相关感染治疗选择有限的挑战。外排介导的抗生素耐药性是一个重大障碍，主要原因是缺乏专门设计用于靶向细菌外排泵的药物。最近的研究已确定多酚类物质（一类广泛的植物源有机化合物）是外排泵活性的潜在抑制剂。本综述汇总了关于八种广泛分布的多酚类物质（姜黄素、槲皮素、木犀草素、单宁酸、柚皮素、表没食子儿茶素-3-没食子酸酯、鞣花酸和白藜芦醇）抑制特性的数据。这些化合物已证明有能力抑制外排泵，要么通过直接干扰细菌蛋白质功能，要么通过下调编码泵亚基的基因表达。重要的是，几种多酚类物质与抗生素（包括黏菌素、环丙沙星和四环素）表现出协同相互作用。例如，槲皮素已显示出与维拉帕米和利血平之类已确立的外排泵抑制剂相当的抑制效力。这些发现表明，多酚类物质是开发新型外排泵抑制剂的有前景的候选物。然而，需要进一步研究以验证它们的有效性和安全性，并促进其转化为对抗抗生素耐药性的临床应用。
