Novel mutations for CLR resistance of H. pylori. Helicobacter pylori 26695-1CL

Resistance to clarithromycin (CLR) is the most important factor in failed Helicobacter pylori eradication. Two types of CLR-resistant strains (low- and high-resistant strains) were obtained from CLR-sensitive H. pylori exposed to low CLR concentrations. High-resistant strains contained well-known mutations in 23S ribosomal RNA (rRNA; A2143G), whereas low-resistant strains did not. Next-generation sequencing identified 7 candidate mutations related to CLR resistance in 23S rRNA. The natural transformants containing mutations in hp1048, hp1314 (9-bp insertion or 3-bp deletion), and 23S rRNA in wild-type strain 26695 showed low-to-moderate resistance to CLR. Transformants containing double mutations mutation in 23S rRNA and mutations in hp1048 or hp1314 showed higher resistance. Next-generation sequencing is a useful tool for screening mutations related to drug resistance. We discovered novel mutations related to CLR resistance (hp1048 and hp1314) that have synergic effects with 23S rRNA.