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Infection and Immunity, October 1999, p. 5361-5366, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Phase Variation in Helicobacter pylori Lipopolysaccharide due to Changes in the Lengths of Poly(C) Tracts in alpha 3-Fucosyltransferase Genes

Ben J. Appelmelk,1,* Steve L. Martin,2 Mario A. Monteiro,3 Chris A. Clayton,2 Andrew A. McColm,2 Pengyuan Zheng,1,dagger Theo Verboom,1 Janneke J. Maaskant,1 Dirk H. van den Eijnden,4 Cornelis H. Hokke,4 Malcolm B. Perry,3 Christina M. J. E. Vandenbroucke-Grauls,1 and Johannes G. Kusters1

Departments of Medical Microbiology1 and Medical Chemistry,4 Vrije Universiteit, Medical School, 1081 BT Amsterdam, The Netherlands; Glaxo Wellcome Medicines Research Centre, Stevenage, United Kingdom2; and Institute of Biological Sciences, National Research Council, Ottawa, Canada3

Received 11 March 1999/Returned for modification 15 June 1999/Accepted 16 July 1999

The lipopolysaccharide (LPS) of Helicobacter pylori expresses the Lewis x (Lex) and/or Ley antigen. We have shown previously that H. pylori LPS displays phase variation whereby an Lex-positive strain yields variants with different LPS serotypes, for example, Lex plus Ley or nonfucosylated polylactosamine. H. pylori has two alpha 3-fucosyltransferase genes that both contain poly(C) tracts. We now demonstrate that these tracts can shorten or lengthen randomly, which results in reversible frameshifting and inactivation of the gene products. We provide genetic and serological evidence that this mechanism causes H. pylori LPS phase variation and demonstrate that the on or off status of alpha 3-fucosyltransferase genes determines the LPS serotypes of phase variants and clinical isolates. The role of the alpha 3-fucosyltransferase gene products in determining the LPS serotype was confirmed by structural-chemical analysis of alpha 3-fucosyltransferase knockout mutants. The data also show that the two alpha 3-fucosyltransferase genes code for enzymes with different fine specificities, and we propose the names futA and futB to designate the orthologs of the H. pylori 26695 alpha 3-fucosyltransferase genes HP0379 and HP0651, respectively. The data also show that the alpha 3-fucosylation in H. pylori precedes alpha 3-fucosyltransferase, an order of events opposite to that which prevails in mammals. Finally, the data provide an understanding at the molecular level of the mechanisms underlying LPS diversity in H. pylori, which may play an important role in adaptation to the host.

* Corresponding author. Mailing address: Department of Medical Microbiology, Vrije Universiteit, Med. School, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Phone: 31 20 4448297. Fax: 31 20 4448318. E-mail: BJ.Appelmelk.mm{at}med.vu.nl.

dagger Present address: Department of Digestive Diseases, Second Affiliated Hospital, Henan Medical University, Zhengzhou, People's Republic of China.

Infection and Immunity, October 1999, p. 5361-5366, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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