A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach.

Autor:	Winter JA; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Letley DP; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Cook KW; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Rhead JL; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Zaitoun AA; Department of Pathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, United Kingdom., Ingram RJ; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Amilon KR; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Croxall NJ; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Kaye PV; Department of Pathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, United Kingdom., Robinson K; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham., Atherton JC; Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2014 Sep 15; Vol. 210 (6), pp. 954-63. Date of Electronic Publication: 2014 Mar 12.
DOI:	10.1093/infdis/jiu154
Abstrakt:	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. (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)
Databáze:	MEDLINE
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