title: Functional plasticity in the type IV secretion system of Helicobacter pylori.
abstract: Helicobacter pylori causes clinical disease primarily in those individuals infected with a strain that carries the cytotoxin associated gene pathogenicity island (cagPAI). The cagPAI encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into epithelial cells and is required for induction of the pro-inflammatory cytokine, interleukin-8 (IL-8). CagY is an essential component of the H. pylori T4SS that has an unusual sequence structure, in which an extraordinary number of direct DNA repeats is predicted to cause rearrangements that invariably yield in-frame insertions or deletions. Here we demonstrate in murine and non-human primate models that immune-driven host selection of rearrangements in CagY is sufficient to cause gain or loss of function in the H. pylori T4SS. We propose that CagY functions as a sort of molecular switch or perhaps a rheostat that alters the function of the T4SS and "tunes" the host inflammatory response so as to maximize persistent infection.
authors.affiliation: Center for Comparative Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Barrozo
authors.forename: Cara L
authors.initials: CL
authors.lastname: Cooke
authors.forename: Lori M
authors.initials: LM
authors.lastname: Hansen
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lam
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Johnson
authors.forename: Taryn A
authors.initials: TA
authors.lastname: Cariaga
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
authors.forename: Jay V
authors.initials: JV
authors.lastname: Solnick
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000502:physiology*; D004269:DNA, Bacterial; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D054884:Host-Pathogen Interactions; D016209:Interleukin-8 / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011995:Recombination, Genetic; D013047:Specific Pathogen-Free Organisms; D037521:Virulence Factors
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D004269:DNA, Bacterial; D016209:Interleukin-8; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori