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

Mol Microbiol. 2018 Dec;110(5):761-776. doi: 10.1111/mmi.14123. Epub 2018 Oct 25.


The human gastric pathogen Helicobacter pylori occurs in two basic variants, either exhibiting a functional cagPAI-encoded type-4-secretion-system (T4SS) or not. Only a few cagPAI-positive strains have been successfully adapted for long-term infection of mice, including the pre-mouse Sydney strain 1 (PMSS1). Here we confirm that PMSS1 induces gastric inflammation and neutrophil infiltration in mice, progressing to intestinal metaplasia. Complete genome analysis of PMSS1 revealed 1,423 coding sequences, encompassing the cagPAI gene cluster and, unusually, the location of the cytotoxin-associated gene A (cagA) approximately 15 kb downstream of the island. PMSS1 harbours three genetically exchangeable loci that are occupied by the hopQ coding sequences. HopQ represents a critical co-factor required for the translocation of CagA into the host cell and activation of NF-κB via the T4SS. Long-term colonisation of mice led to an impairment of cagPAI functionality. One of the bacterial clones re-isolated at four months post-infection revealed a mutation in the cagPAI gene cagW, resulting in a frame shift mutation, which prevented CagA translocation, possibly due to an impairment of T4SS function. Rescue of the mutant cagW re-established CagA translocation. Our data reveal intriguing insights into the adaptive abilities of PMSS1, suggesting functional modulation of the H. pylori cagPAI virulence attribute.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Cell Line, Tumor
  • Female
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Multigene Family
  • Type IV Secretion Systems / genetics*
  • Virulence
  • Whole Genome Sequencing / methods


  • Bacterial Proteins
  • Type IV Secretion Systems