Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands

Area of Science:

• Microbiology
• Gastroenterology
• Molecular Biology

Background:

• Chronic Helicobacter pylori infection is a major risk factor for gastric cancer.
• H. pylori adaptation to changing host tissue environments during disease progression is not fully understood.
• Gastric metaplasia involves altered protein expression, such as TFF3, and represents a pre-cancerous change.

Purpose of the Study:

• To investigate how H. pylori adapts to the changing gastric environment during disease development.
• To identify bacterial factors involved in colonizing metaplastic gastric glands.
• To understand the role of adhesins in H. pylori persistence and disease progression.

Main Methods:

• Utilized a transgenic mouse model of gastric metaplasia.
• Tested H. pylori strains from different disease stages and individuals for colonization ability.
• Performed whole-genome sequencing and targeted gene mutation (sabB) to assess adherence and colonization.

Main Results:

• H. pylori strains from later disease stages exhibited enhanced colonization of metaplastic glands.
• A unique variation in the adhesin gene sabB, arising from recombination with sabA, was identified in late-stage strains.
• Mutation of sabB significantly reduced bacterial adherence to gastric tissue and attenuated stomach colonization in mice.

Conclusions:

• The changing gastric environment during H. pylori infection selects for bacterial genetic variations, specifically in adhesin genes.
• The adhesin SabB plays a critical role in H. pylori adherence and colonization of the diseased stomach.
• Genomic diversification of H. pylori, including sabB variation, is a key factor for bacterial persistence and stomach cancer development.