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Infection and Immunity, December 2001, p. 7334-7340, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7334-7340.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Phase Variation in the Helicobacter pylori Phospholipase A Gene and Its Role in Acid Adaptation

Tone Tannæs,1,2,*,dagger Niek Dekker,3 Geir Bukholm,1,dagger Jetta J. E. Bijlsma,2 and Ben J. Appelmelk2

Institute of Medical Microbiology, University of Oslo, Oslo, Norway,1 and Department of Enzymology and Protein Engineering, Utrecht University, Utrecht,3 and Department of Medical Microbiology, Vrije Universiteit, Amsterdam,2 The Netherlands

Received 20 February 2001/Returned for modification 20 April 2001/Accepted 31 August 2001

Previously, we have shown that Helicobacter pylori can spontaneously and reversibly change its membrane lipid composition, producing variants with low or high content of lysophospholipids. The "lyso" variant contains a high percentage of lysophospholipids, adheres better to epithelial cells, and releases more proteins such as urease and VacA, compared to the "normal" variant, which has a low content of lysophospholipids. Prolonged growth of the normal variant at pH 3.5, but not under neutral conditions, leads to enrichment of lyso variant colonies, suggesting that the colony switch is relevant to acid adaptation. In this study we show that the change in membrane lipid composition is due to phase variation in the pldA gene. A change in the (C) tract length of this gene results in reversible frameshifts, translation of a full-length or truncated pldA, and the production of active or inactive outer membrane phospholipase A (OMPLA). The role of OMPLA in determining the colony morphology was confirmed by the construction of an OMPLA-negative mutant. Furthermore, variants with an active OMPLA were able to survive acidic conditions better than variants with the inactive form. This explains why the lyso variant is selected at low pH. Our studies demonstrate that phase variation in the pldA gene, resulting in an active form of OMPLA, is important for survival under acidic conditions. We also demonstrated the active OMPLA genotype in fresh isolates of H. pylori from patients referred to gastroscopy for dyspepsia.

* Corresponding author. Mailing address: Department of Infection Control, Akershus University Central Hospital, N-1474 Nordbyhagen, Norway. Phone: 47-67929323. Fax: 47-67928278. E-mail: tone_tannas{at}hotmail.com.

dagger Present address: Department of Infection Control, Akershus University Central Hospital, Nordbyhagen, Norway.

Infection and Immunity, December 2001, p. 7334-7340, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7334-7340.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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