Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori

Hitoshi Tsugawa; Hidekazu Suzuki; Hiroe Muraoka; Fumiaki Ikeda; Kenro Hirata; Juntaro Matsuzaki; Yoshimasa Saito; Toshifumi Hibi

doi:10.1016/j.bbrc.2010.12.034

Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori

Hitoshi Tsugawa, Hidekazu Suzuki, Hiroe Muraoka, Fumiaki Ikeda, Kenro Hirata, Juntaro Matsuzaki, Yoshimasa Saito, Toshifumi Hibi

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

Abstract

Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori.

Original language	English
Pages (from-to)	656-660
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	404
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2010.12.034
Publication status	Published - 2011 Jan 14

Keywords

Antimicrobial agent
Drug resistance
Efflux pump
HefA
RdxA

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2010.12.034

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title = "Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori",

abstract = "Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori.",

keywords = "Antimicrobial agent, Drug resistance, Efflux pump, HefA, RdxA",

author = "Hitoshi Tsugawa and Hidekazu Suzuki and Hiroe Muraoka and Fumiaki Ikeda and Kenro Hirata and Juntaro Matsuzaki and Yoshimasa Saito and Toshifumi Hibi",

note = "Funding Information: This work supported by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) ( 21790133 , to H.T.), a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (JSPS) ( 22300169 , to H.S.), a grant from the Smoking Research Foundation (to H.S.) and Keio University Research grants for Life Sciences and Medicine ( 99-095-0009 , to H.T.).",

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AU - Tsugawa, Hitoshi

AU - Suzuki, Hidekazu

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AU - Ikeda, Fumiaki

AU - Hirata, Kenro

AU - Matsuzaki, Juntaro

AU - Saito, Yoshimasa

AU - Hibi, Toshifumi

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PY - 2011/1/14

Y1 - 2011/1/14

N2 - Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori.

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Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori

Abstract

Keywords

ASJC Scopus subject areas

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