Ratti Alessandro, Fassi Enrico M A, Forlani Fabio, Mori Matteo, Villa Federica, Cappitelli Francesca, Sgrignani Jacopo, Roda Gabriella, Cavalli Andrea, Villa Stefania, Grazioso Giovanni
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy.
Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente, Via G. Celoria 2, 20133 Milano, Italy.
Pharmaceutics. 2023 Jun 17;15(6):1757. doi: 10.3390/pharmaceutics15061757.
Bacterial biofilm is a major contributor to the persistence of infection and the limited efficacy of antibiotics. Antibiofilm molecules that interfere with the biofilm lifestyle offer a valuable tool in fighting bacterial pathogens. Ellagic acid (EA) is a natural polyphenol that has shown attractive antibiofilm properties. However, its precise antibiofilm mode of action remains unknown. Experimental evidence links the NADH:quinone oxidoreductase enzyme WrbA to biofilm formation, stress response, and pathogen virulence. Moreover, WrbA has demonstrated interactions with antibiofilm molecules, suggesting its role in redox and biofilm modulation. This work aims to provide mechanistic insights into the antibiofilm mode of action of EA utilizing computational studies, biophysical measurements, enzyme inhibition studies on WrbA, and biofilm and reactive oxygen species assays exploiting a WrbA-deprived mutant strain of . Our research efforts led us to propose that the antibiofilm mode of action of EA stems from its ability to perturb the bacterial redox homeostasis driven by WrbA. These findings shed new light on the antibiofilm properties of EA and could lead to the development of more effective treatments for biofilm-related infections.
细菌生物膜是感染持续存在和抗生素疗效有限的主要原因。干扰生物膜生活方式的抗生物膜分子为对抗细菌病原体提供了一种有价值的工具。鞣花酸（EA）是一种天然多酚，已显示出具有吸引人的抗生物膜特性。然而，其确切的抗生物膜作用模式仍不清楚。实验证据将NADH：醌氧化还原酶WrbA与生物膜形成、应激反应和病原体毒力联系起来。此外，WrbA已证明与抗生物膜分子相互作用，表明其在氧化还原和生物膜调节中的作用。这项工作旨在利用计算研究、生物物理测量、对WrbA的酶抑制研究以及利用缺失WrbA的突变菌株进行的生物膜和活性氧测定，来深入了解EA的抗生物膜作用机制。我们的研究工作使我们提出，EA的抗生物膜作用模式源于其扰乱由WrbA驱动的细菌氧化还原稳态的能力。这些发现为EA的抗生物膜特性提供了新的见解，并可能导致开发出更有效的生物膜相关感染治疗方法。
