Global Population Structure, Virulence Factors and Antibiotic Resistance of Helicobacter pylori: A Pooled Analysis of 4067 Isolates From 76 Countries

Helicobacter pylori (H. pylori) is a common pathogen that has co-evolved with the human host for approximately 100,000 years; however, our understanding of its population structure remains limited. Furthermore, the detailed characteristics of its virulence factors and antibiotic resistance for H. pylori are not yet fully elucidated. In this study, we curated a global genome dataset of 4067 H. pylori isolates from 76 countries and explored H. pylori characteristics, including population genetic structure, virulence factors, and antibiotic resistance. We used three approaches (fineSTRUCTURE, ADMIXTURE, and DAPC) to infer the population structure of H. pylori. We investigated the virulence of each isolate by calling genotypes of cagA and vacA and evaluated the correlations of virulence factors with subpopulation. For antibiotic resistance, we identified mutations to determine the genotypic antibiotic resistance. Then we estimated the prevalence of genotypic antibiotic resistance grouped by geographical location, subpopulation, and study period. We identified 21 subpopulations in 4067 H. pylori isolates, including 20 previously reported subpopulations and a novel subpopulation hspEuropeIsrael, and found that the population structure of H. pylori was geographically restricted. The novel subpopulation hspEuropeIsrael had a higher proportion of less virulent cagA and vacA genotypes compared to other subpopulations. After evaluating the rates of H. pylori genotypic resistance to four antibiotics, we found that the prevalence of genotypic resistance to amoxicillin and metronidazole was > 15% across all five continents. Genotypic resistance to levofloxacin was > 15% on all continents except for Oceania. Additionally, the genotypic resistance rate to clarithromycin was > 15% in Asia, Europe, and Oceania. A trend of increased genotypic resistance over time was observed in several continents during subgroup analyses. Furthermore, we constructed a comprehensive database for H. pylori, named Helicobacter Pylori Encyclopedia for Research (HELPER, http://ccra.njmu.edu.cn/helper). Our results provide a detailed characterization of H. pylori and extend previous schemas. HELPER serves as an informative and comprehensive database that will be a valuable resource for researchers and lay the foundation for future studies on H. pylori.