title: FecA1, a bacterial iron transporter, determines the survival of Helicobacter pylori in the stomach.
abstract: 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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Juntaro
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Kenro
authors.initials: K
authors.lastname: Hirata
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D007501:Iron / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008795:Metronidazole / Q000627:therapeutic use; D017384:Sequence Deletion / Q000235:genetics; D013270:Stomach / Q000382:microbiology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D008795:Metronidazole; D007501:Iron; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase