Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells

• H. pylori impairs the DNA repair response in normal human epithelial cells
• Distinct genomic regions show increased susceptibility to H. pylori-induced damage
• DNA damage accumulates in telomere-proximal, actively transcribed regions
• Susceptible genomic regions overlap with gastric cancer genomic aberrations

SummaryInfection with the human pathogen Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.

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