Nordihydroguaiaretic Acid Disrupts the Antioxidant Ability ofHelicobacter pylorithrough the Repression of SodB ActivityIn Vitro

Abstract

Iron-cofactored superoxide dismutase (SodB) ofHelicobacter pyloriplays an indispensable role in the bacterium’s colonization of the stomach. Previously, we demonstrated that FecA1, a Fe3+-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe2+) to SodB, andfecA1-deletion mutant strains have reduced gastric mucosal-colonization ability in Mongolian gerbils, suggesting that FecA1 is a possible target for the development of a novel eradication therapy. This study aimed to identify novel FecA1-binding compoundsin silicoand then examined the effect of a predicted FecA1-binding compound onH. pyloriSodB activityin vitro. Specifically, we demonstrated that nordihydroguaiaretic acid (NDGA) is a predicted FecA1-binding compound. NDGA reduced intracellular Fe2+levels inH. pyloriand reduced SodB activity. Additionally, NDGA increased H2O2sensitivity ofH. pyloriand increased the metronidazole (Mtz) sensitivity. The present study demonstrated that NDGA repressed SodB activity associated with the gastric mucosal-colonization via inhibition of intracellular Fe2+uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.