Potent Inhibition of Bacterial DNA Gyrase by Digallic Acid and Other Gallate Derivatives

Abstract

Bacterial DNA gyrase, an essential enzyme, is a validated target for discovering and developing new antibiotics. Here we screened a pool of polyphenols and discovered that digallic acid is a potent DNA gyrase inhibitor. We also found that several food additives based on gallate, such as dodecyl gallate, potently inhibit bacterial DNA gyrase. Interestingly, the IC50 of these gallate derivatives against DNA gyrase is correlated with the length of hydrocarbon chain connecting to the gallate. These new bacterial DNA gyrase inhibitors are ATP competitive inhibitors of DNA gyrase. Our results also show that digallic acid and certain gallate derivatives potently inhibit E. coli DNA topoisomerase IV. Several gallate derivatives have strong antimicrobial activities against Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus (MRSA). This study provides a solid foundation for the design and synthesis of gallate‐based DNA gyrase inhibitors that may be used to combat antibacterial resistance.

Berry and Grape Metabolites for Antimicrobial Applications Against Foodborne Bacterial Pathogens

“…It is considered that Gram-negative bacteria are more resistant to the effects of antioxidants, due to the presence of the lipophilic outer membrane formed by phospholipids, which makes the cell wall of these bacteria impermeable. Moreover, it is believed that Gram-negative bacteria can chemically degrade polyphenols by their enzymes [37].…”

“…One of the mechanisms of antimicrobial action of antioxidants consists in their interaction with cell wall proteins, which has the effect of damaging bacterial membranes and their permeabilization, loss of chemiosmotic control, leakage of intracellular components and eventual cell death [37,38]. Other recent studies emphasize the inhibitory properties of polyphenols in relation to biofilm production by bacteria [39].…”