Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Free Radic Biol Med. 2012 Mar 15;52(6):1003-10. doi: 10.1016/j.freeradbiomed.2011.12.011. Epub 2011 Dec 23.
Helicobacter pylori encodes a single iron-cofactored superoxide dismutase (SodB), which is regulated by the ferric uptake regulator (Fur). Ferrous ion (Fe(2+)) is necessary for the activation of SodB. The activity of SodB is an important determinant of the capability of H. pylori for long-term colonization of the stomach and of the development of metronidazole (Mtz) resistance of the bacterium. This study is conducted to characterize the Fe(2+)-supply mechanisms for the activation of SodB in H. pylori, which, as mentioned above, is associated with the host-colonization ability and Mtz resistance of H. pylori. In this study, we demonstrate that fecA1, a Fe(3+)-dicitrate transporter homolog, is an essential gene for SodB activation, but not for the biogenic activity of H. pylori. H. pylori with SodB inactivation by fecA1 deletion showed reduced resistance to H(2)O(2), reduced gastric mucosal-colonization ability in Mongolian gerbils, and also reduced resistance to Mtz. Our experiment demonstrated that FecA1 is an important determinant of the host-colonization ability and Mtz resistance of H. pylori through Fe(2+) supply to SodB, suggesting that FecA1 may be a possible target for the development of a novel bactericidal drug.
幽门螺杆菌编码一种单一的含铁超氧化物歧化酶（SodB），其受亚铁摄取调节剂（Fur）调控。亚铁离子（Fe(2+)）是 SodB 激活所必需的。SodB 的活性是幽门螺杆菌长期定植胃和产生甲硝唑（Mtz）耐药性的重要决定因素。本研究旨在描述幽门螺杆菌中 SodB 激活的铁供应机制，如上所述，这与幽门螺杆菌的宿主定植能力和 Mtz 耐药性有关。在本研究中，我们证明了 fecA1，一种 Fe(3+)-二柠檬酸转运体同源物，是 SodB 激活的必需基因，但不是幽门螺杆菌生物活性的必需基因。通过 fecA1 缺失使 SodB 失活的幽门螺杆菌对 H2O2 的抵抗力降低，在蒙古沙土鼠中的胃黏膜定植能力降低，对 Mtz 的耐药性也降低。我们的实验表明，FecA1 通过向 SodB 供应 Fe(2+)，成为幽门螺杆菌宿主定植能力和 Mtz 耐药性的重要决定因素，表明 FecA1 可能是开发新型杀菌药物的潜在靶点。
