title: A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach.
abstract: Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gastric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and inflammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cagPAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA(+) background.
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Jody A
authors.initials: JA
authors.lastname: Winter
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Darren P
authors.initials: DP
authors.lastname: Letley
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Cook
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Rhead
authors.affiliation: Department of Pathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, United Kingdom.
authors.forename: Abed A M
authors.initials: AA
authors.lastname: Zaitoun
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Richard J M
authors.initials: RJ
authors.lastname: Ingram
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Karin R
authors.initials: KR
authors.lastname: Amilon
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Croxall
authors.affiliation: Department of Pathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, United Kingdom.
authors.forename: Phillip V
authors.initials: PV
authors.lastname: Kaye
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: Karen
authors.initials: K
authors.lastname: Robinson
authors.affiliation: Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
authors.forename: John C
authors.initials: JC
authors.lastname: Atherton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001427:Bacterial Toxins / Q000378:metabolism*; D005260:Female; D016481:Helicobacter Infections / Q000473:pathology*; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008297:Male; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013270:Stomach / Q000382:microbiology* / Q000473:pathology; D014617:Vacuoles / Q000473:pathology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C074689:VacA protein, Helicobacter pylori
keywords: Helicobacter pylori; SPEM; colonization; gastric cancer; pathogenesis; virulence