A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Winter, JA ORCID: 0000-0003-3582-7596, Letley, D P, Cook, K W, Rhead, J L, Zaitoun, A A M, Ingram, R J M, Amilon, K R, Croxall, N J, Kaye, P V, Robinson, K and Atherton, J C, 2014. A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach. Journal of Infectious Diseases, 210 (6), pp. 954-963. ISSN 0022-1899

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Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric 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 in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI 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.

Item Type: Journal article
Publication Title: Journal of Infectious Diseases
Creators: Winter, J.A., Letley, D.P., Cook, K.W., Rhead, J.L., Zaitoun, A.A.M., Ingram, R.J.M., Amilon, K.R., Croxall, N.J., Kaye, P.V., Robinson, K. and Atherton, J.C.
Publisher: Oxford University Press
Date: 2014
Volume: 210
Number: 6
ISSN: 0022-1899
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 02 Nov 2015 16:15
Last Modified: 09 Jun 2017 13:56
URI: http://irep.ntu.ac.uk/id/eprint/26097

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