Genomic features of the Helicobacter pylori strain PMSS1 and its virulence attributes as deduced from its in vivo...

Area of Science:

• Microbiology
• Pathogenesis
• Bacterial Genetics

Background:

• Helicobacter pylori is a human gastric pathogen with two variants: those with and without a functional cagPAI-encoded type-4-secretion-system (T4SS).
• Few cagPAI-positive strains, like pre-mouse Sydney strain 1 (PMSS1), adapt to long-term mouse infection.
• PMSS1 induces gastric inflammation, neutrophil infiltration, and intestinal metaplasia in mice.

Purpose of the Study:

• To investigate the genomic characteristics and adaptive capabilities of H. pylori strain PMSS1 during long-term mouse infection.
• To understand the role of the cagPAI gene cluster and its components, such as CagA and HopQ, in H. pylori pathogenesis and adaptation.
• To identify genetic modifications in H. pylori that occur during prolonged host colonization.

Main Methods:

• Complete genome analysis of H. pylori strain PMSS1.
• Infection of mice with PMSS1 to study pathogenesis and long-term colonization.
• Isolation and genetic analysis of bacterial clones re-isolated from infected mice.
• Functional rescue experiments to confirm the role of specific mutations.

Main Results:

• PMSS1 genome analysis revealed 1,423 coding sequences, including the cagPAI and a downstream cagA gene.
• PMSS1 possesses three exchangeable loci for the hopQ gene, a co-factor for CagA translocation and NF-κB activation.
• Long-term mouse colonization led to impaired cagPAI functionality, evidenced by a cagW mutation causing a frame shift, preventing CagA translocation.
• Rescue of the cagW mutation restored CagA translocation, confirming its critical role.

Conclusions:

• H. pylori strain PMSS1 demonstrates significant adaptive abilities in a mouse model, modulating its cagPAI virulence attributes.
• Functional impairment of the cagPAI system, specifically through mutations like in cagW, is a key adaptive mechanism during prolonged infection.
• These findings provide insights into the dynamic interplay between H. pylori virulence factors and host adaptation, impacting pathogenesis.