Zhu Mengyi, Xu Xianfeng, Cai Pengpeng, Wang Tianpei, Zhu Meng, Yan Caiwang, Pan Qianglong, Chen Chen, Wu Ying, Zhang Guoxin, Jin Guangfu
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Helicobacter. 2025 Mar-Apr;30(2):e70025. doi: 10.1111/hel.70025.
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.
幽门螺杆菌是一种常见病原体，与人类宿主共同进化了约10万年；然而，我们对其种群结构的了解仍然有限。此外，幽门螺杆菌毒力因子和抗生素耐药性的详细特征尚未完全阐明。
在本研究中，我们整理了来自76个国家的4067株幽门螺杆菌分离株的全球基因组数据集，并探索了幽门螺杆菌的特征，包括种群遗传结构、毒力因子和抗生素耐药性。我们使用三种方法（fineSTRUCTURE、ADMIXTURE和DAPC）来推断幽门螺杆菌的种群结构。我们通过对cagA和vacA的基因型进行分型来研究每个分离株的毒力，并评估毒力因子与亚群的相关性。对于抗生素耐药性，我们通过鉴定突变来确定基因型抗生素耐药性。然后，我们估计了按地理位置、亚群和研究时期分组的基因型抗生素耐药性的流行率。
我们在4067株幽门螺杆菌分离株中鉴定出21个亚群，包括20个先前报道的亚群和一个新的亚群hspEuropeIsrael，并发现幽门螺杆菌的种群结构受地理限制。与其他亚群相比，新的亚群hspEuropeIsrael中低毒力的cagA和vacA基因型比例更高。在评估幽门螺杆菌对四种抗生素的基因型耐药率后，我们发现五大洲对阿莫西林和甲硝唑的基因型耐药率均>15%。除大洋洲外，其他各大洲对左氧氟沙星的基因型耐药率均>15%。此外，亚洲、欧洲和大洋洲对克拉霉素的基因型耐药率>15%。在亚组分析中，几个大洲观察到基因型耐药性随时间增加的趋势。此外，我们构建了一个针对幽门螺杆菌的综合数据库，名为幽门螺杆菌研究百科全书（HELPER，http://ccra.njmu.edu.cn/helper）。
我们的结果提供了幽门螺杆菌的详细特征，并扩展了先前的模式。HELPER是一个信息丰富且全面的数据库，将为研究人员提供宝贵资源，并为未来幽门螺杆菌研究奠定基础。
