title: [Study of infection strategies of Helicobacter pylori and host cell response against CagA oncoprotein].
abstract: Chronic infection with Helicobacter pylori is involved in a variety of clinical outcomes including gastric cancer. In the present study, we focused on the infection strategies of H. pylori associated with establishment of chronic infection. As a result, the following four findings revealed. 1) alpha-ketoglutarate oxidoreductase (KOR) is an essential survival enzyme for energy metabolism in the coccoid form of H. pylori, and inactivation of the KOR activity exerted a potent bactericidal action against H. pylori by preventing induction of the coccoid form. 2) SodB expression is derepressed by amino acids mutation of ferric uptake regulator (Fur), which is associated with the development of Metronidazole resistance. 3) FecA1 is an important determinant of the host-colonization ability through Fe(2+) supply to SodB, suggesting that FecA1 may be a possible target for the development of a novel bactericidal drug. 4) Intracellular CagA oncoprotein is degraded by autophagy and therefore short lived. However, in the CD44v9-expressing gastric cells, CagA specifically accumulated through the repression of autophagy induction.
authors.affiliation: Department of Biochemistry & Integrative Medical Biology, School of Medicine, Keio University.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000942:Antigens, Bacterial / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054316:Biomarkers, Pharmacological; D002952:Citric Acid Cycle / Q000502:physiology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology; D009154:Mutation; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology; D013386:Succinates / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000596:Amino Acids; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D054316:Biomarkers, Pharmacological; D007656:Ketoglutaric Acids; D012097:Repressor Proteins; D013386:Succinates; C080866:cagA protein, Helicobacter pylori; C068477:ferric uptake regulating proteins, bacterial; D008795:Metronidazole; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase