Nordihydroguaiaretic Acid Disrupts the Antioxidant Ability of Helicobacter pylori through the Repression of SodB Activity In Vitro

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.