The intermediate region of Helicobacter pylori VacA is a determinant of toxin potency in a Jurkat T cell assay.

Infection and Immunity
Christian González-RiveraTimothy L Cover

Abstract

Colonization of the human stomach with Helicobacter pylori is a risk factor for peptic ulceration, noncardia gastric adenocarcinoma, and gastric lymphoma. The secreted VacA toxin is an important H. pylori virulence factor that causes multiple alterations in gastric epithelial cells and T cells. Several families of vacA alleles have been described, and H. pylori strains containing certain vacA types (s1, i1, and m1) are associated with an increased risk of gastric disease, compared to strains containing other vacA types (s2, i2, and m2). Thus far, there has been relatively little study of the role of the VacA intermediate region (i-region) in toxin activity. In this study, we compared the ability of i1 and i2 forms of VacA to cause functional alterations in Jurkat cells. To do this, we manipulated the chromosomal vacA gene in two H. pylori strains to introduce alterations in the region encoding the VacA i-region. We did not detect any differences in the capacity of i1 and i2 forms of VacA to cause vacuolation of RK13 cells. In comparison to i1 forms of VacA, i2 forms of VacA had a diminished capacity to inhibit the activation of nuclear factor of activated T cells (NFAT) and suppress interleukin-2 (IL-2) production. Correspondin...Continue Reading

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Citations

Oct 26, 2013·Trends in Microbiology·Laura K Greenfield, Nicola L Jones
Dec 5, 2014·Clinical and Experimental Medicine·Batool MottaghiMohammad Hossein Somi
Sep 18, 2013·Helicobacter·Manuel KochSteven F Moss
Sep 18, 2013·Helicobacter·Trinidad Parra CidNicola L Jones
Nov 28, 2012·Journal of Molecular Biology·Melissa G ChambersMelanie D Ohi
Aug 31, 2013·Gut Microbes·Timothy L Cover, Richard M Peek
Jun 15, 2016·Toxins·Tran Thi Huyen TrangYoshio Yamaoka
Jun 9, 2016·Toxins·Nora J FoegedingTimothy L Cover
Jun 17, 2016·Molecular Microbiology·Tasia M PyburnMelanie D Ohi
Dec 11, 2014·Memórias do Instituto Oswaldo Cruz·Lucia Libanez Bessa Campelo BragaDulciene Maria Magalhães Queiroz
Oct 13, 2017·Toxins·Mark S McClainTimothy L Cover
May 1, 2020·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Asif SukriNik Ritza Kosai
Apr 15, 2020·Infection and Immunity·Rhonda R CastonTimothy L Cover
Apr 8, 2019·Journal of Molecular Biology·Min SuMelanie D Ohi
Jul 16, 2021·Critical Reviews in Microbiology·Radwa N MorganMohammad M Aboulwafa

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