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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroe
authors.initials: H
authors.lastname: Muraoka
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ikeda
authors.forename: Kenro
authors.initials: K
authors.lastname: Hirata
authors.forename: Juntaro
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Saito
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D004151:Dipeptides / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008795:Metronidazole / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D004151:Dipeptides; C419365:phenylalanine arginine beta-naphthylamide; D008795:Metronidazole