Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori

Kenro Hirata, Hidekazu Suzuki, Toshihiro Nishizawa, Hitoshi Tsugawa, Hiroe Muraoka, Yoshimasa Saito, Juntaro Matsuzaki, Toshifumi Hibi

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background and Aims: Although clarithromycin (CLR) is one of the most commonly recommended component drugs of Helicobacter pylori eradication regimens, the prevalence of CLR-resistant H. pylori has been increasing. It is well known that CLR resistance is associated with point mutations in 23S rRNA, but an active multidrug efflux mechanism of H. pylori may also play a role in its drug resistance. At least four gene clusters have been identified as efflux pump systems in H. pylori and the present study was designed to investigate their role in the CLR resistance of clinical isolates of H. pylori. Methods: Fifteen CLR-resistant H. pylori strains (minimal inhibitory concentration [MIC] ≥ 1 μg/mL) isolated from patients at Keio University Hospital were examined for expression of efflux pump mRNA by real-time polymerase chain reaction. In addition, the MIC of CLR in the presence or absence of Phe-Arg-β-naphthylamide (PAβN), an efflux pump inhibitor (EPI), were determined. Results: In all 15 strains, efflux pump mRNA was expressed, and the MIC of CLR were decreased by using EPI, despite possessing 23s rRNA point mutations. In addition, the MIC of CLR was decreased by the EPI in a concentration-dependent fashion. Conclusion: The efflux pump of H. pylori is associated with the development of resistance to CLR, in addition to 23S rRNA point mutations. Efflux pumps could be a novel target for reversing drug resistance in H. pylori.

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume25
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2010

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Clarithromycin
Helicobacter pylori
Point Mutation
Drug Resistance
Messenger RNA
Multigene Family
Real-Time Polymerase Chain Reaction

Keywords

  • Clarithromycin
  • Efflux pump
  • Helicobacter pylori
  • Phe-Arg-β-naphthylamide

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology
  • Medicine(all)

Cite this

Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori. / Hirata, Kenro; Suzuki, Hidekazu; Nishizawa, Toshihiro; Tsugawa, Hitoshi; Muraoka, Hiroe; Saito, Yoshimasa; Matsuzaki, Juntaro; Hibi, Toshifumi.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 25, No. SUPPL. 1, 2010.

Research output: Contribution to journalArticle

Hirata, Kenro ; Suzuki, Hidekazu ; Nishizawa, Toshihiro ; Tsugawa, Hitoshi ; Muraoka, Hiroe ; Saito, Yoshimasa ; Matsuzaki, Juntaro ; Hibi, Toshifumi. / Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori. In: Journal of Gastroenterology and Hepatology (Australia). 2010 ; Vol. 25, No. SUPPL. 1.
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