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Originally published In Press as doi:10.1074/jbc.M108574200 on December 7, 2001

J. Biol. Chem., Vol. 277, Issue 8, 5785-5795, February 22, 2002
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Phenotypic Variation in Molecular Mimicry between Helicobacter pylori Lipopolysaccharides and Human Gastric Epithelial Cell Surface Glycoforms
ACID-INDUCED PHASE VARIATION IN LEWISX AND LEWISY EXPRESSION BY H. PYLORI LIPOPOLYSACCHARIDES*

Anthony P. MoranDagger , Yuriy A. Knirel§, Sof'ya N. Senchenkova§, Göran Widmalm||, Sean O. HynesDagger , and Per-Erik Jansson§**

From the Dagger  Department of Microbiology, National University of Ireland, Galway, Ireland, § Karolinska Institute, Clinical Research Centre, Huddinge University Hospital, Novum, S-141 86 Huddinge, Sweden,  N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia, and || Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-10691 Stockholm, Sweden

Helicobacter pylori is an important gastroduodenal pathogen of humans whose survival in the gastric environment below pH 4 is dependent on bacterial production of urease, whereas above pH 4 urease-independent mechanisms are involved in survival, but that remain to be elucidated fully. Previous structural investigations on the lipopolysaccharides (LPSs) of H. pylori have shown that the majority of these surface glycolipids express partially fucosylated, glucosylated, or galactosylated N-acetyllactosamine (LacNAc) O-polysaccharide chains containing Lewisx (Lex) and/or Lewisy (Ley), although some strains also express type 1 determinants, Lewisa, Lewisb, and H-1 antigen. In this study, we investigated acid-induced changes in the structure and composition of LPS and cellular lipids of the genome-sequenced strain, H. pylori 26695. When grown in liquid medium at pH 7, the O-chain consisted of a type 2 LacNAc polysaccharide, which was glycosylated with alpha -L-fucose at O-3 of the majority of N-acetylglucosamine residues forming Lex units, including chain termination by a Lex unit. However, growth in liquid medium at pH 5 resulted in production of a more complex O-chain whose backbone of type 2 LacNAc units was partially glycosylated with alpha -L-fucose, thus forming Lex, whereas the majority of the nonfucosylated N-acetylglucosamine residues were substituted at O-6 by alpha -D-galactose residues, and the chain was terminated by a Ley unit. In contrast, detailed chemical analysis of the core and lipid A components of LPS and analysis of cellular lipids did not show significant differences between H. pylori 26695 grown at pH 5 and 7. Although putative molecular mechanisms affecting Lex and Ley expression have been investigated previously, this is the first report identifying an environmental trigger inducing phase variation of Lex and Ley in H. pylori that can aid adaptation of the bacterium to its ecological niche.


* This work was supported by The International Association for the Promotion of Cooperation with Scientists from the New Independent States of the Former Soviet Union Grant 97-0695, Irish Health Research Board (to A. P. M.), Millennium Research Fund (to A. P. M.), Swedish Research Council (to P. E. J. and G. W.), Royal Swedish Academy of Sciences (to P. E. J.), and Karolinska Institute fellowships (to Y. A. K. and S. N. S.). This work was presented in part at the 19th International Carbohydrate Symposium, August 9-14, 1998 in San Diego, CA.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed. Tel.: 46-8-58583821; Fax: 46-8-58583820; E-mail: pererik.jansson@kfc.hs.sll.se.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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