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

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Winter, J.A. 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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Official URL: http://dx.doi.org/10.1093/infdis/jiu154

Abstract

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:

ISSN:

0022-1899

Identifiers: