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

• Published in: Scientific reports 2024-08, Vol.14 (1), p.20108-10, Article 20108
• Main Authors: Starkova, Daria, Gladyshev, Nikita, Polev, Dmitrii, Saitova, Alina, Egorova, Svetlana, Svarval, Alena
• Format: Article
• Language: English
• Subjects: 631/208/325; 631/208/737; 631/337; Adult; Aged; Anti-Bacterial Agents - pharmacology; Antibiotics; Clarithromycin; Clarithromycin - pharmacology; Clinical isolates; Drug resistance; Drug Resistance, Bacterial - genetics; Female; Frameshift mutation; Gene deletion; Genetic diversity; Genetic Variation; Genome, Bacterial; Helicobacter Infections - drug therapy; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - drug effects; Helicobacter pylori - genetics; Humanities and Social Sciences; Humans; Male; Microbial Sensitivity Tests; Middle Aged; multidisciplinary; Mutation; Nucleotide sequence; Phenotypic variations; RNA, Ribosomal, 23S - genetics; rRNA; rRNA 23S; Russia - epidemiology; Science; Science (multidisciplinary); Sequence analysis; Virulence; Whole Genome Sequencing - methods
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70977-4

Clarithromycin (CLR) is currently a key antibiotic for Helicobacter pylori infection treatment, however, the data on CLR resistance patterns in Russia are missing. Here, we applied WGS-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variation, identify putative markers of CLR resistance and correlate them with phenotypic susceptibility testing. The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method: 23 isolates were CLR-resistant and 21-CLR-susceptible. All isolates were subjected to WGS and submitted to GenBank. Based on complete sequence analysis, we showed that among all sequence variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic susceptibility. For the first time, the average number of mutations in 106 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 a frameshift deletion (252:CGGGT) in HP0820 coding region, which is a good candidate for further investigation.