Whole-genome sequencing of clarithromycin resistant Helicobacter pylori characterizes unidentified variants of multidrug resistant efflux pump genes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: The University of Tokushima (2016); Kobe Pharmaceutical University (2014-2015)
• Principal Investigator: TANAHASHI Toshihito 徳島大学, 大学院医歯薬学研究部(医学系), 学術研究員 (30380067)
• Research Collaborator: AZUMA Takeshi 神戸大学, 医学部, 教授 ; OKADA Rina 神戸大学, 医学部, 技術補佐員 ; TAGUCHI Yoshihiro 中央大学, 理工学部, 教授
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 全ゲノムシークエンシング / ヘリコバクターピロリ菌 / 薬剤耐性 / クラリスロマイシン

Outline of Final Research Achievements

Clarithromycin (CLR) is the key drug in eradication therapy of Helicobacter pylori (H. pylori) infection, and widespread use of CLR has led to an increase in primary CLR-resistant H. pylori. The known mechanism of CLR resistance has been established in A2146G and A2147G mutations in the 23S rRNA gene, but evidence of the involvement of other genetic mechanisms is lacking. Using the MiSeq platform, whole-genome sequencing of the 19 clinical strains and the reference strain ATCC26695 was performed. All sequencing reads of CLR-resistant strains had a G mutation in an identical position of the 23S rRNA gene. In addition, genetic variants of four gene clusters (hp0605-hp0607, hp0971-hp0969, hp1327-hp1329, and hp1489-hp1487) of TolC homologues, which have been implicated in multi-drug resistance, were examined. Gene clusters of TolC homologues are involved in CLR susceptibility profiles in individual H. pylori strains.

Free Research Field

消化器内科学