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Infection and Immunity, August 2001, p. 5080-5087, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.5080-5087.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Vacuolating Cytotoxin of Helicobacter pylori Induces Apoptosis in the Human Gastric Epithelial Cell Line AGS

Dirk Kuck,1 Bernhard Kolmerer,2 Christof Iking-Konert,1 Peter H. Krammer,3 Wolfgang Stremmel,1 and Jochen Rudi1,*

Department of Medicine, University of Heidelberg, 69115 Heidelberg,1 European Molecular Biology Laboratory, 69012 Heidelberg,2 and German Cancer Research Center, 69120 Heidelberg,3 Germany

Received 17 July 2000/Returned for modification 18 October 2000/Accepted 18 April 2001

Helicobacter pylori induces cell death by apoptosis. However, the apoptosis-inducing factor is still unknown. The virulence factor vacuolating cytotoxin A (VacA) is a potential candidate, and thus its role in apoptosis induction was investigated in the human gastric epithelial cell line AGS. The supernatant from the vacA wild-type strain P12 was able to induce apoptotic cell death, whereas the supernatant from its isogenic mutant strain P14 could not. That VacA was indeed the apoptosis-inducing factor was demonstrated further by substantial reduction of apoptosis upon treatment of AGS cells with a supernatant specifically depleted of native VacA. Furthermore, a recombinant VacA produced in Escherichia coli was also able to induce apoptosis in AGS cells but failed to induce cellular vacuolation. These findings demonstrate that the vacuolating cytototoxin of H. pylori is a bacterial factor capable of inducing apoptosis in gastric epithelial cells.

* Corresponding author. Present address: Department of Medicine, Division of Gastroenterology, Theresienkrankenhaus Mannheim, Bassermannstr. 1, 68165 Mannheim, Germany. Phone: 49-621-4244306. Fax: 49-621-4244663. E-mail: J.Rudi{at}t-online.de.

Infection and Immunity, August 2001, p. 5080-5087, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.5080-5087.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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