Mechanistic Insights into the Antibiofilm Mode of Action of Ellagic Acid

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 Escherichia coli. 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.

Automated summary

Bacterial biofilm is a major cause of persistent infection and antibiotic resistance. This study investigates the antibiofilm properties and mode of action of ellagic acid (EA), a natural polyphenol. The researchers propose that EA disrupts the bacterial redox homeostasis mediated by the NADH:quinone oxidoreductase enzyme WrbA, leading to its antibiofilm activity. These findings provide new insights into the potential use of EA for treating biofilm-related infections.