Exploration of the molecular mechanisms underlying the antibiotic resistance of Helicobacter pylori: A whole‐genome sequencing‐based study in Southern China

Although antimicrobial resistance (AMR) in Helicobacter pylori is a global threat to human health and the underlying molecular mechanisms have been explored previously, only a few of them are fully elucidated.In the present study, we isolated 54 Helicobacter pylori strains from Southern China and assessed their susceptibility to five antibiotics using the agar dilution assay. Whole-genome sequencing was performed to screen the AMR genotypes of the Helicobacter pylori isolates.Our study revealed a high prevalence of resistance to clarithromycin (CLR), levofloxacin (LVX), and metronidazole (MTZ) in the Chinese isolates, 55.56% of which showed multidrug-resistant phenotypes. We screened for the 94 types of previously reported AMR mutations in 12 genes, but only a few of them were related to the AMR phenotype. Furthermore, we discovered four new mutations in the 23S rRNA gene and one mutation in infB related to CLR resistance. Another three mutations in gyrA and one in gyrB were closely correlated with the AMR pattern against LVX. We also demonstrated that the mutations R16C/H in rdxA, V56I in rpsU, and D54A in sodB might contribute to resistance to MTZ, which were previously reported in laboratory experiments but not found in clinical strains. We examined the concordance between the genotype and phenotype of AMR and identified several potential molecular biomarkers for predicting CLR and LVX resistance.Our study explored the molecular mechanisms underlying the antibiotic resistance of Helicobacter pylori isolates from Southern China. We propose further epidemiologic investigations in China.