FecA1, a bacterial iron transporter, determines the survival of Helicobacter pylori in the stomach

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• 作者：Hitoshi Tsugawa ; Hidekazu Suzuki ; ^{hsuzuki@a6.keio.jp} ; Juntaro Matsuzaki ; Kenro Hirata ; Toshifumi Hibi
• 关键词：FecA1 ; ferric citrate transporter homolog protein ; Fur ; ferric uptake regulator ; Mtz ; metronidazole ; ROS ; reactive oxygen species ; SodB ; iron-cofactored superoxide dismutase
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 出版时间：15 March 2012
• 年：2012
• 卷：52
• 期：6
• 页码：1003-1010
• 全文大小：928 K

文摘

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 H₂O₂, 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.