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

Winter, Jody; Letley, Darren; Cook, Katherine; Rhead, Joanne; Zaitoun, Abed; Ingram, Richard; Amilon, Karin; Croxall, Nicola; Kaye, Phillip; Robinson, Karen; Atherton, John

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.

Citation

Winter, J., Letley, D., Cook, K., Rhead, J., Zaitoun, A., Ingram, R., …Atherton, J. (2014). A role for the vacuolating cytotoxin, VacA, in colonisation and Helicobacter pylori-induced metaplasia in the stomach. Journal of Infectious Diseases, 210(6), 954–963. https://doi.org/10.1093/infdis/jiu154

• Journal Article Type: Article
• Acceptance Date: Mar 3, 2014
• Online Publication Date: Mar 12, 2014
• Publication Date: Sep 15, 2014
• Deposit Date: Sep 6, 2017
• Publicly Available Date: Oct 15, 2018
• Print ISSN: 0022-1899
• Electronic ISSN: 1537-6613
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 210
• Issue: 6
• Pages: 954–963
• DOI: https://doi.org/10.1093/infdis/jiu154
• Keywords: Gastric cancer; Pathogenesis; SPEM; Helicobacter pylori; Virulence; Colonization
• Public URL: http://jid.oxfordjournals.org/content/early/2014/03/12/infdis.jiu154.abstract
• Publisher URL: https://academic.oup.com/jid/article/210/6/954/2908513