4.6 Article

FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity

期刊

FEBS JOURNAL
卷 281, 期 19, 页码 4495-4505

出版社

WILEY-BLACKWELL
DOI: 10.1111/febs.12958

关键词

Helicobacter pylori; nitroreductase; nitrosative stress; nitrosoglutathione; S-nitrosoglutathione (GSNO) reductase

资金

  1. Fundacao para a Ciencia e Tecnologia [PEst-OE/EQB/LA0004/2011, PTDC/BBB-BQB/0937/2012, SFRH/BD/81192/2011]
  2. Fundação para a Ciência e a Tecnologia [PTDC/BBB-BQB/0937/2012, SFRH/BD/81192/2011] Funding Source: FCT

向作者/读者索取更多资源

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.

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