Two amino acids mutation of ferric uptake regulator determines helicobacter pylori resistance to metronidazole

Hitoshi Tsugawa, Hidekazu Suzuki, Kazue Satoh, Kenro Hirata, Juntaro Matsuzaki, Yoshimasa Saito, Makoto Suematsu, Toshifumi Hibi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Metronidazole (Mtz) is a prodrug that is converted to its active form when its nitro group is reduced and superoxide radicals are generated. The superoxide radicals are directly toxic to the bacterium. On the other hand, the transcriptional regulator, ferric uptake regulator (Fur), of Helicobacter pylori is a direct suppressor of the iron-cofactored superoxide dismutase SodB, which is essential for protection against superoxide attack. Here, we demonstrate that in some Mtz-resistant strains, SodB activity is induced in a dose-dependent manner on exposure to Mtz. Further, under Mtz exposure, the generation of superoxide radicals in Mtz-resistant strains was significantly reduced as compared with that in the Mtz-susceptible strains. These Mtz-resistant strains were found to carry amino acids mutation of Fur (C78Y, P114S; mutant-type Fur). The binding affinity of the mutant-type Fur to an operator sequence on the sodB promoter (Fur-Box) was significantly reduced. Our approach demonstrated that SodB expression is derepressed by mutant-type Fur, which is associated with the development of Mtz resistance.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalAntioxidants and Redox Signaling
Volume14
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Metronidazole
Helicobacter pylori
Amino Acids
Mutation
Superoxides
Poisons
Prodrugs
Superoxide Dismutase
Bacteria

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Two amino acids mutation of ferric uptake regulator determines helicobacter pylori resistance to metronidazole. / Tsugawa, Hitoshi; Suzuki, Hidekazu; Satoh, Kazue; Hirata, Kenro; Matsuzaki, Juntaro; Saito, Yoshimasa; Suematsu, Makoto; Hibi, Toshifumi.

In: Antioxidants and Redox Signaling, Vol. 14, No. 1, 01.01.2011, p. 15-23.

Research output: Contribution to journalArticle

Tsugawa, Hitoshi ; Suzuki, Hidekazu ; Satoh, Kazue ; Hirata, Kenro ; Matsuzaki, Juntaro ; Saito, Yoshimasa ; Suematsu, Makoto ; Hibi, Toshifumi. / Two amino acids mutation of ferric uptake regulator determines helicobacter pylori resistance to metronidazole. In: Antioxidants and Redox Signaling. 2011 ; Vol. 14, No. 1. pp. 15-23.
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