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

► The metronidazole (Mtz)-resistance was induced under sub-inhibitory concentrations of Mtz exposure. ► The initial step in the acquisition of Mtz resistance is the overexpression of bacterial efflux system ( hefA). ► The MICs of Mtz-resistance-induced strains were decreased in the presence of efflu...

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Published in:Biochemical and biophysical research communications 2011-01, Vol.404 (2), p.656-660
Main Authors: Tsugawa, Hitoshi, Suzuki, Hidekazu, Muraoka, Hiroe, Ikeda, Fumiaki, Hirata, Kenro, Matsuzaki, Juntaro, Saito, Yoshimasa, Hibi, Toshifumi
Format: Article
Language:English
Subjects:
Anti-Infective Agents - metabolism
Anti-Infective Agents - pharmacology
Antimicrobial agent
Bacteria
Bacterial Outer Membrane Proteins - antagonists & inhibitors
Bacterial Outer Membrane Proteins - genetics
Dipeptides - pharmacology
Drug resistance
Drug Resistance, Bacterial - genetics
Efflux pump
HefA
Helicobacter pylori
Helicobacter pylori - drug effects
Helicobacter pylori - genetics
Helicobacter pylori - metabolism
metronidazole
Metronidazole - metabolism
Metronidazole - pharmacology
RdxA
Transcription, Genetic
transporters
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Summary:► The metronidazole (Mtz)-resistance was induced under sub-inhibitory concentrations of Mtz exposure. ► The initial step in the acquisition of Mtz resistance is the overexpression of bacterial efflux system ( hefA). ► The MICs of Mtz-resistance-induced strains were decreased in the presence of efflux pump inhibitor. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.12.034