Premium
Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori
Author(s) -
Hirata Kenro,
Suzuki Hidekazu,
Nishizawa Toshihiro,
Tsugawa Hitoshi,
Muraoka Hiroe,
Saito Yoshimasa,
Matsuzaki Juntaro,
Hibi Toshifumi
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2009.06220.x
Subject(s) - efflux , 23s ribosomal rna , clarithromycin , helicobacter pylori , microbiology and biotechnology , drug resistance , point mutation , medicine , multiple drug resistance , antibiotics , gene , biology , mutation , biochemistry , gastroenterology , rna , ribosome
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 .