First insight into the whole-genome sequence variations in clarithromycin- resistant Helicobacter pylori clinical isolates in Russia

Abstract

Clarithromycin (CLR) is a key drug to treat Helicobacter pylori infection, however the data on CLR resistance patterns in Russia are missing. Here, we applied next-generation sequencing (NGS)-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variations, identify putative markers of CLR resistance and correlate them with phenotypic drug susceptibility testing (DST). The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method. All isolates were undergone whole-genome sequencing and submitted to GenBank. Twenty-three H. pylori isolates were phenotypically CLR-resistant and 21- were CLR-susceptible. Based on complete sequence analysis, we showed that among all genetic variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic DST. For the first time, the average number of nucleotide variants in 108 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was frameshift deletion in HP0820 coding region, which is a good candidate for further investigation.