Global genomic landscape of antimicrobial resistance in Helicobacter pylori: Large-scale analysis of resistance genes, lineages, and evolutionary trajectories.
TL;DR
This large-scale global genomic study demonstrates the extensive dissemination and ongoing evolution of AMR in H. pylori, particularly against amoxicillin and fluoroquinolones, and indicates that empirical treatment strategies based on these agents are becoming increasingly unsustainable worldwide.
Abstract
Background
Antimicrobial resistance (AMR) in Helicobacter pylori is increasingly compromising eradication therapies worldwide. Despite growing concern, comprehensive global genomic analyses integrating resistance determinants, geographic distribution, and evolutionary patterns remain limited.
Methods
A total of 6876 high-quality H. pylori genomes collected from 85 countries between 1900 and 2024 were analyzed. Resistance determinants were identified using AMRFinderPlus, followed by lineage profiling, geographic mapping, temporal trend analysis, and resistome characterization. The distribution of virulence-associated genes and resistance gene presence patterns was also evaluated.
Results
Twenty-two AMR determinants were identified, predominantly chromosomal mutations. The most prevalent mutation was pbp1a S543R, associated with amoxicillin resistance, detected in 24.03% (1652/6876) of genomes across 63 countries since 1983. Fluoroquinolone resistance-associated gyrA N87K demonstrated a marked temporal increase, reaching approximately 50% prevalence by 2023. Additional gyrA and pbp1a variants were widely distributed globally. Acquired resistance genes, including blaTEM,aph(3')-IIIa, and catA1, were rare and primarily confined to sequence type 181. Among 2877 resistant isolates, 103 distinct resistance profiles were observed, with single-mutation patterns predominating. Geographic analysis revealed pbp1a S543R prevalence exceeding 40% in multiple Asian and African countries, while gyrA N87K exceeded 30% in parts of Asia and South America. The resistome exhibited an open structure, whereas 134 virulence-associated genes remained highly conserved.
Conclusions
This large-scale global genomic study demonstrates the extensive dissemination and ongoing evolution of AMR in H. pylori, particularly against amoxicillin and fluoroquinolones. The findings indicate that empirical treatment strategies based on these agents are becoming increasingly unsustainable worldwide. Implementation of susceptibility-guided therapy, rapid molecular diagnostics, and international genomic surveillance programs is urgently required to preserve eradication efficacy and limit further resistance expansion.