title: Dynamics of the Cag-type IV secretion system of Helicobacter pylori as studied by bacterial co-infections.
abstract: Many pathogenic Gram-negative bacteria possess type IV secretion systems (T4SS) to inject effector proteins directly into host cells to modulate cellular processes to their benefit. The human bacterial pathogen Helicobacter pylori, a major aetiological agent in the development of chronic gastritis, duodenal ulcer and gastric carcinoma, harbours the cag-T4SS to inject the cytotoxin associated Antigen (CagA) into gastric epithelial cells. This results in deregulation of major signalling cascades, actin-cytoskeletal rearrangements and eventually gastric cancer. We show here that a pre-infection with live H. pylori has a dose-dependent negative effect on the CagA translocation efficiency of a later infecting strain. This effect of the 'first' strain was independent of any of its T4SS, the vacuolating cytotoxin (VacA) or flagella. Other bacterial pathogens, e.g. pathogenic Escherichia coli, Campylobacter jejuni, Staphylococcus aureus, or commensal bacteria, such as lactobacilli, were unable to interfere with H. pylori's CagA translocation capacity in the same way. This interference was independent of the β1 integrin receptor availability for H. pylori, but certain H. pylori outer membrane proteins, such as HopI, HopQ or AlpAB, were essential for the effect. We suggest that the specific interference mechanism induced by H. pylori represents a cellular response to restrict and control CagA translocation into a host cell to control the cellular damage.
authors.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University, Pettenkoferstraße 9a, D-80336, Munich, Germany.
authors.forename: Luisa F
authors.initials: LF
authors.lastname: Jiménez-Soto
authors.forename: Sabine
authors.initials: S
authors.lastname: Clausen
authors.forename: Annika
authors.initials: A
authors.lastname: Sprenger
authors.forename: Claudia
authors.initials: C
authors.lastname: Ertl
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
mesh_terms: D000898:Antibiosis; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000502:physiology; D006801:Humans; D021381:Protein Transport
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C080866:cagA protein, Helicobacter pylori