title: FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity.
abstract: Helicobacter pylori is a pathogen that infects the gastric mucosa of a large percentage of the human population worldwide, and predisposes to peptic ulceration and gastric cancer. Persistent colonization of humans by H. pylori triggers an inflammatory response that leads to the production of reactive nitrogen species. However, the mechanisms of H. pylori defence against nitrosative stress remain largely unknown. In this study, we show that the NADH-flavin oxidoreductase FrxA of H. pylori, besides metabolizing nitrofurans and metronidazole, has S-nitrosoglutathione reductase activity. In agreement with this, inactivation of the FrxA-encoding gene resulted in a strain that was more sensitive to S-nitrosoglutathione. FrxA was also shown to contribute to the proliferation of H. pylori in macrophages, which are key phagocytic cells of the mammalian innate immune system. Moreover, FrxA was shown to support the virulence of the pathogen upon mouse infection. Altogether, we provide evidence for a new function of FrxA that contributes to the successful chronic colonization ability that characterizes H. pylori.
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal; Escola Superior de Tecnologia do Barreiro, Instituto Politécnico de Setúbal, Barreiro, Portugal.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Justino
authors.forename: Margarida R
authors.initials: MR
authors.lastname: Parente
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Lígia M
authors.initials: LM
authors.lastname: Saraiva
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry* / Q000502:physiology; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology; D001483:Base Sequence; D004790:Enzyme Induction; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity; D007700:Kinetics; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability; D009574:Nitro Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D026422:S-Nitrosoglutathione / Q000737:chemistry / Q000494:pharmacology; D013312:Stress, Physiological; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D009574:Nitro Compounds; D026422:S-Nitrosoglutathione; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent
keywords: Helicobacter pylori; S-nitrosoglutathione (GSNO) reductase; nitroreductase; nitrosative stress; nitrosoglutathione