High resolution electron microscopy of the Helicobacter pylori Cag type IV secretion system pili produced in varying conditions of iron availability

J Vis Exp. 2014 Nov 21:(93):e52122. doi: 10.3791/52122.

Abstract

Helicobacter pylori is a helical-shaped, gram negative bacterium that colonizes the human gastric niche of half of the human population. H. pylori is the primary cause of gastric cancer, the second leading cause of cancer-related deaths worldwide. One virulence factor that has been associated with increased risk of gastric disease is the Cag-pathogenicity island, a 40-kb region within the chromosome of H. pylori that encodes a type IV secretion system and the cognate effector molecule, CagA. The Cag-T4SS is responsible for translocating CagA and peptidoglycan into host epithelial cells. The activity of the Cag-T4SS results in numerous changes in host cell biology including upregulation of cytokine expression, activation of proinflammatory pathways, cytoskeletal remodeling, and induction of oncogenic cell-signaling networks. The Cag-T4SS is a macromolecular machine comprised of sub-assembly components spanning the inner and outer membrane and extending outward from the cell into the extracellular space. The extracellular portion of the Cag-T4SS is referred to as the "pilus". Numerous studies have demonstrated that the Cag-T4SS pili are formed at the host-pathogen interface(. However, the environmental features that regulate the biogenesis of this important organelle remain largely obscure. Recently, we reported that conditions of low iron availability increased the Cag-T4SS activity and pilus biogenesis. Here we present an optimized protocol to grow H. pylori in varying conditions of iron availability prior to co-culture with human gastric epithelial cells. Further, we present the comprehensive protocol for visualization of the hyper-piliated phenotype exhibited in iron restricted conditions by high resolution scanning electron microscopy analyses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Video-Audio Media

MeSH terms

  • Epithelial Cells / microbiology
  • Fimbriae, Bacterial / metabolism*
  • Fimbriae, Bacterial / ultrastructure*
  • Gastric Mucosa / cytology
  • Gastric Mucosa / microbiology
  • Genomic Islands
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / metabolism*
  • Helicobacter pylori / ultrastructure*
  • Humans
  • Iron / metabolism*
  • Microscopy, Electron / methods
  • Signal Transduction
  • Type IV Secretion Systems / biosynthesis*
  • Type IV Secretion Systems / metabolism
  • Type IV Secretion Systems / ultrastructure*
  • Virulence Factors / metabolism

Substances

  • Type IV Secretion Systems
  • Virulence Factors
  • Iron