Identification of the Helicobacter pylori VacA Toxin Domain Active in the Cell Cytosol

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Infection and Immunity, December 1998, p. 6014-6016, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of the Helicobacter pylori VacA Toxin Domain Active in the Cell Cytosol

Marina de Bernard,¹ Daniela Burroni,² Emanuele Papini,¹ Rino Rappuoli,² John Telford,² and Cesare Montecucco¹^,^*

Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, 35121 Padova¹ and Centro Ricerche IRIS, CHIRON-Biocine Vaccines, 53100 Siena,² Italy

Received 22 June 1998/Returned for modification 10 August 1998/Accepted 22 September 1998

Cells exposed to Helicobacter pylori toxin VacA develop large vacuoles which originate from massive swelling of membranouscompartments at late stages of the endocytic pathway. When expressedin the cytosol, VacA induces vacuolization as it does when addedfrom outside. This and other evidence indicate that VacA is atoxin capable of entering the cell cytosol, where it displaysits activity. In this study, we have used cytosolic expressionto identify the portion of the toxin molecule responsible forthe vacuolating activity. VacA mutants with deletions at the Cand N termini were generated, and their activity was analyzedupon expression in HeLa cells. We found that the vacuolating activityof VacA resides in the amino-terminal region, the whole of whichis required for its intracellularactivity.

^* Corresponding author. Mailing address: Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova,Via G. Colombo 3, 35121 Padva, Italy. Phone: 39-49-8276058. Fax:39-49-8276049. E-mail: cesare{at}civ.bio.unipd.it.

Infection and Immunity, December 1998, p. 6014-6016, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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