Helicobacter pylori resistance in Hainan Province, China: investigating phenotypes and genotypes through whole-genome sequencing

Front Cell Infect Microbiol. 2024 Dec 17:14:1505166. doi: 10.3389/fcimb.2024.1505166. eCollection 2024.

Abstract

Helicobacter pylori is increasingly resistant to antibiotics, significantly lowering eradication rates and posing a major public health challenge. This study investigated the distribution of antibiotic-resistant phenotypes and genotypes of H. pylori in Hainan Province. It determined the minimum inhibitory concentrations (MICs) of six antibiotics using the E-test method and detected resistance genes via Sanger sequencing. Furthermore, we compared resistance detection based on phenotypic analysis and whole genome sequencing (WGS) across 19 clinical isolates of H. pylori. A total of 140 H. pylori strains were isolated. The resistance rates to levofloxacin (LEV), clarithromycin (CLA), and metronidazole (MTZ) were 37.9%, 40.0%, and 93.6%, respectively. Notably, only 3.3% of the strains were susceptible to all six antibiotics. Multidrug-resistant strains accounted for 25.0% of the total, with no resistance detected to amoxicillin (AMX), tetracycline (TET), or furazolidone (FR) during the study period. Genotypic resistance to CLA and LEV showed near-perfect concordance with phenotypic resistance, with Kappa values of 0.910 and 0.938, respectively. Although all isolates were phenotypically sensitive to TET, 16 exhibited a mutation in the 16S rRNA gene (A926G). All strains harboring the R16H/C mutation and truncated rdxA were resistant to metronidazole, demonstrating a specificity of 100%. Therefore, FR, AMX, and TET are recommended as suitable empirical treatment options for H. pylori infections in this region. Genotypic analysis provides a reliable method for predicting resistance to CLA and LEV. WGS proves to be a valuable tool for identifying novel resistance loci in H. pylori and contributes to the phylogenetic classification of strains.

Keywords: Helicobacter pylori; antibiotic resistance; genotypic; lineage; phenotypic; whole-genome sequencing.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents* / pharmacology
  • China / epidemiology
  • Clarithromycin / pharmacology
  • Drug Resistance, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Genome, Bacterial / genetics
  • Genotype*
  • Helicobacter Infections* / microbiology
  • Helicobacter pylori* / drug effects
  • Helicobacter pylori* / genetics
  • Helicobacter pylori* / isolation & purification
  • Humans
  • Male
  • Metronidazole / pharmacology
  • Microbial Sensitivity Tests*
  • Middle Aged
  • Phenotype*
  • Whole Genome Sequencing*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Metronidazole
  • Clarithromycin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Clinical Key Speciality Capacity Building Project (No. 202330), Hainan Province Clinical Medical Center (No. 2021818), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202313), Joint Project on Health Science and Technology Innovation in Hainan Province (WSJK2024MS150), Hainan Provincial Postgraduate Innovation Research Project (Qhyb2022-133), and Hainan Provincial Teaching Reform Project (hnjg2024-67).