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<p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is a globally prevalent gastric pathogen with substantial genetic diversity shaped by human co-evolution. Although extensive research has been conducted on <i>H. pylori</i>, the mechanisms underlying its adaptation and virulence remain incompletely understood. Here, we performed a phylogenomic analysis of 1467 isolates from 26 countries by constructing a core-genome single-nucleotide polymorphism (SNP) phylogeny and analyzing population structure, revealing five major lineages with distinct regional adaptations. A genome-wide Fixation Index (Fst) analysis identified 20 highly differentiated genes, with cagE (Fst = 0.8041)—a key component of the Type IV Secretion System (T4SS)—showing the strongest signal of positive selection. We discovered a novel N792D mutation in <i>cagE</i>, fixed in cluster c1, particularly in North America, which may enhance immune evasion and promote persistent colonization. Bayesian Evolutionary Analysis Sampling Trees 2 (BEAST2) analysis estimated that the most recent common ancestor (tMRCA) of highly virulent <i>H. pylori</i> emerged around 1934 (95% HPD: 1933–1934), coinciding with global conflicts and migrations that likely facilitated its spread. This study provides new insights into <i>H. pylori</i> evolution, highlighting the <i>cagE</i> mutation as a potential therapeutic target.</p>

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Global phylogenomic insights into the evolutionary adaptation of Helicobacter pylori: evidence from 1467 isolates and the fixation of cage D792 mutation

  • 期刊论文

  • 发表日期：

    2025年12月5日

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  • Shenke Zhang,
  • Lianghui Peng,
  • Boyu Liao,
  • Cuixian Yang,
  • Jingjie Song,
  • Zeeshan Umar,
  • Shengli Zhang,
  • Liqiu Ma,
  • Rui Liu

摘要

Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen with substantial genetic diversity shaped by human co-evolution. Although extensive research has been conducted on H. pylori, the mechanisms underlying its adaptation and virulence remain incompletely understood. Here, we performed a phylogenomic analysis of 1467 isolates from 26 countries by constructing a core-genome single-nucleotide polymorphism (SNP) phylogeny and analyzing population structure, revealing five major lineages with distinct regional adaptations. A genome-wide Fixation Index (Fst) analysis identified 20 highly differentiated genes, with cagE (Fst = 0.8041)—a key component of the Type IV Secretion System (T4SS)—showing the strongest signal of positive selection. We discovered a novel N792D mutation in cagE, fixed in cluster c1, particularly in North America, which may enhance immune evasion and promote persistent colonization. Bayesian Evolutionary Analysis Sampling Trees 2 (BEAST2) analysis estimated that the most recent common ancestor (tMRCA) of highly virulent H. pylori emerged around 1934 (95% HPD: 1933–1934), coinciding with global conflicts and migrations that likely facilitated its spread. This study provides new insights into H. pylori evolution, highlighting the cagE mutation as a potential therapeutic target.