Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro

Abstract

Iron-cofactored superoxide dismutase (SodB) of Helicobacter pylori plays an indispensable role in the bacterium's colonization of the stomach. Previously, we demonstrated that FecA1, a Fe 3+ -dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe 2+) to SodB, and fecA1-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 compounds in silico and then examined the effect of a predicted FecA1-binding compound on H. pylori SodB activity in vitro. Specifically, we demonstrated that nordihydroguaiaretic acid (NDGA) is a predicted FecA1-binding compound. NDGA reduced intracellular Fe 2+ levels in H. pylori and reduced SodB activity. Additionally, NDGA increased H 2 O 2 sensitivity of H. pylori and increased the metronidazole (Mtz) sensitivity. The present study demonstrated that NDGA repressed SodB activity associated with the gastric mucosal-colonization via inhibition of intracellular Fe 2+ uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.