title: Helicobacter pylori entry into human gastric epithelial cells: A potential determinant of virulence, persistence, and treatment failures.
abstract: OBJECTIVE
  Intracellular location of Helicobacter pylori in human gastric epithelial cells has been observed in biopsies. Whether this reflects an ability to invade host cells and establish an intracellular niche remains to be determined.
  
  
  METHODS
  The interactions between a clinical isolate of H. pylori and primary cell cultures from human gastric epithelium or the human epithelial cell line HEp-2 were monitored using time-lapse photography. This technique allows studies of the dynamics of host-microbial interactions.
  
  
  RESULTS
  H. pylori cells readily approached and established close contacts with epithelial cells followed by uptake of the bacteria into the cellular cytoplasm. Entry into epithelial cells was achieved through an active process of bacterial motility and penetration of the cell membranes. In conventional invasion assays using HEp-2 cells, an increased internalization in a strain producing the vacuolating cytotoxin was observed, compared to the isogenic VacA knockout mutant.
  
  
  CONCLUSIONS
  Invasion of gastric epithelium represents a hitherto unappreciated trait of H. pylori that could contribute to the bacterium's ability to establish persistent infection that evades the mucosal immune defense and sometimes also antimicrobial therapy. A small number of bacterial cells with a transient intracellular habitat could serve as a seeder population, providing a backup for a constantly challenged and fluctuating luminal population.
authors.affiliation: Department of Clinical Microbiology, University Hospital, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Björkholm
authors.forename: V
authors.initials: V
authors.lastname: Zhukhovitsky
authors.forename: C
authors.initials: C
authors.lastname: Löfman
authors.forename: K
authors.initials: K
authors.lastname: Hultén
authors.forename: H
authors.initials: H
authors.lastname: Enroth
authors.forename: M
authors.initials: M
authors.lastname: Block
authors.forename: R
authors.initials: R
authors.lastname: Rigo
authors.forename: P
authors.initials: P
authors.lastname: Falk
authors.forename: L
authors.initials: L
authors.lastname: Engstrand
mesh_terms: D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D009154:Mutation; D010781:Photography / Q000379:methods; D017211:Treatment Failure; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori